The invention relates to the fields of molecular biology, cell biology and dermatology. More specifically, the invention relates to the molecular events underlying the response of a cell to exposure to ultraviolet radiation and, thereby, to the molecular processes contributing towards the development of premature tissue aging and cancer.
Human skin is relatively simple tissue that performs varied and complex functions such as temperature regulation, the processing of vitamin D precursors, the excretion of urea, and the storage of carbohydrate and fat. The skin contains many unique cell types to effect its specialized functions. On a gross level, the skin consists of epidermis and a basement membrane zone overlying dermis and subcutaneous fat. Skin tissue arises embryologically from ectoderm, neuroectoderm, and mesoderm. The epidermis, hair and sebaceous glands (pilosebaceous units), sweat glands (eccrine units), and nails are all ectodermal derivatives. Neuroectodermal derivatives include melanocytes, nerves, and special neuroreceptors, while mesenchymal derivatives include collagen, reticulin and elastic fibers, blood vessels, muscle, and fat. Probably the most important function of the skin is that of protection; the skin produces a scaling surface impermeable to many substances, has an elaborate network of immunocompetent cells constantly monitoring for potentially harmful antigens, and produces pigment which filters out harmful rays of ultraviolet radiation from the sun.
Ultraviolet radiation is a major environmental damaging agent causing photodamage to the skin, including cutaneous malignancies and photoaging (see generally, Fitzpatrick""s Dermatology in Medicine, Fifth Edition, I. M. Freedberg, et at, eds., McGraw-Hill (1999)). Clinical features of photoaging include wrinkles, skin laxity and coarseness, and pigmentation disorders. While histological manifestations of photoaging have been well known for some time, the molecular mechanisms that cause them have only recently become a focus of concerted studies.
Solar light contains a broad spectrum of energy wavelengths, and ultraviolet radiation which is among the relatively short wavelengths occurring at between 100 and 400 nanometers (in contrast to the visible light spectrum which occurs at between about 490 and 690 nanometers). Ultraviolet radiation is composed of three segments, designated as A, B, and C, Ultraviolet-C radiation (between 100 and 280 nanometers) is filtered out by the earth""s ozone layer and is not known to pose a health threat. There is evidence, however, that exposure to both ultraviolet-A radiation (between 315 and 400 nanometers) and ultraviolet-B radiation (between 280 and 315 nanometers) can have adverse short-term and long-term effects on skin health and visual health. For example, ultraviolet radiation is known to play an important a role in both the development of skin cancers and premature aging of the skin.
The cell type most affected by ultraviolet radiation in humans is the keratinocyte. When illuminated by ultraviolet radiation, the keratinocyte reacts in three generally non-overlapping ways. First, it initiates a DNA repair response, which is activated by the DNA damage itself (Herrlick et al. (1994) Adv. Enzyme Reg. 34:381-95). Second, it signals to the surrounding tissue by releasing pro-inflammatory cytokines, such as IL-1 and TNFxcex1 (Ullrich et al. (2000) J. Dermatol. Sci. 23:S10-2; Ouhtit et al. (2000) Am. J. Pathol. 156:201-7; and Beissert et al. (1999) J. Investig. Dermatol. Symp. Proc. 4:61-4). Third, the keratinocyte activates its inherent responses to ultraviolet radiation by changing its physiology, including regulation of gene expression, cytoskeletal rearrangements, and induction of apoptosis (Zhuang et al. (2000) J. Interferon Cytokine Res. 20:445-54; and Assefa et al. (1997) J. Invest. Dermatol. 108:886-891).
The inherent responses of keratinocytes to ultraviolet radiation, by analogy with responses to other extracellular signals, can be separated into two phases, the immediate and delayed. The immediate phase contains the ultraviolet radiation-specific signal transduction cascades and results in activation of transcription factors. In the delayed phase one sees the changes in gene expression. The invention herein provides a characterization of the ultraviolet radiation-responsive induced and suppressed genes in human epidermal keratinocytes.
The histological signs of photoaging at the epidermal level include the following: (1) variation in the thickness of the epidermis (atrophy or hyperplasia according to the zones observed); (2) a cellular atypia (Kligman et al. (1986) Photodermatol. 3:215-227); (3) a loss of cell polarity; (4) an unevenness of the horny layer; (5) a reduction in the number of Langerhans"" cells (Lavker et al. (1987) J. Invest. Dermatol. 88:44s-51s); (6) a pigmentation characterized by a mosaic appearance with hypo- or hyperpigmentation zones; and (7) a linearization of the dermo-epidermal junction (Lavker (1979) J. Invest. Dermatol. 73:59). For a review of photoaging of the skin, see Gilchourest, Skin and Aging Processes, 1989, CRC Press.
The biologic responses of cells exposed to ultraviolet radiation have been studied in a wide variety of systems, from Esherichia coli to man. In humans, the molecular effects of ultraviolet radiation include DNA damage, apoptosis and activation of the Jun N-terminal kinase (JNK) and the nuclear factor kappa-beta (NFkB). Both studied recently, although not extensively in epidermal keratinocytes, which are the primary target of ultraviolet radiation. A major impetus for studies of the molecular response to ultraviolet radiation came with the identification of the protein kinase that bound to and activated the c-Jun transcription factor in response to ultraviolet radiation (Derijard et al. (1994) Cell 76:1025-1037). The kinase was named xe2x80x9cJNKxe2x80x9d for Jun N-terminal kinase, or xe2x80x9cSAPKxe2x80x9d for stress activated protein kinase (Kyriakis et al. (1994) Nature 369:156-160). Soon it was realized that JNK responds to several extracellular signals in addition to ultraviolet radiation, such as osmotic shock, arsenate, and pro-inflammatory cytokines (Rosette et al. (1996) Science 274:1194-7; Cavigelli et al. (1996) E.M.B.O. Journal 15:6269-79). JNK can phosphorylate additional transcription factors, including Elk1 and ATF2 (Kallunki et al. (1996) Cell 87:929-39). JNK is itself activated by a small number of relatively specific kinases, designated xe2x80x9cJNKKs.xe2x80x9d Many kinases, designated JNKKKs, respond to a large variety of stimuli to phosphorylate and activate xe2x80x9cJNKKs;xe2x80x9d the ultraviolet radiation-responsive JNKKK has not yet been identified (Fanger et al. (1997) Curr. Opin. Genet. Dev. 7:67-74).
Another clear molecular effect of ultraviolet radiation is the activation of the NFkB transcription factor (Devary et al. (1993) Science 261:1442-5). The activation of NFkB by ultraviolet radiation is not associated with DNA damage and occurs even in cytoplasts devoid of nuclear DNA (Devary et al. (1993) Science 261:1442-5; Simon et al. (1994) J. Invest. Dermatol. 102:422-7). Inactive NFkB resides in the cytoplasm complexed with IkB protein. Upon activation by a very large and varied set of extracellular stimuli, IkB is phosphorylated and thus designated for proteolysis. This results in the release of NFkB, which is then free to enter the nucleus and activate gene transcription (Barnes et al. (1997) NE J. Med. 336:1066-71). The ultraviolet radiation-responsive kinases that mark IkB for degradation have not yet been identified (Li et al. (1998) Proc. Natl. Acad. Sci (USA) 95:13012-13017).
Methods to evaluate photodamage to skin or to cells contained therein have been described in the art. For example, U.S. Pat. No. 6,079,415 provides methods and markers useful for establishing ultraviolet-A radiation damage to the dermis, and more specifically, to the production of collagen by fibroblasts of the dermis. Moreover, methods useful for the prevention of ultraviolet radiation damage to the skin or cells contained therein have been described. For example, U.S. Pat. No. 5,908,836 provides methods for protecting skin from ultraviolet radiation damage using sulphated sugars, and U.S. Pat. No. 5,916,880 provides a method to reduce wrinkles by treatment with sulfated sugars. Numerous other examples have been described in the field. For example, U.S. Pat. No. 5,939,457 describes the use of a hydroxy acid product useful for the reduction of wrinkles, U.S. Pat. No. 5,939,082 describes the use of a vitamin B compound for the regulation of signs of skin aging, and U.S. Pat. No. 5,962,534 describes the use of certain retenoids.
However, studies to date examining the response at the molecular level of skin and the specialized skin cells to exposure to ultraviolet radiation almost exclusively have been limited to the examination of one or several genes and/or proteins specific to a particular cellular process. For example, the study by Garmyn et al. ((1991) Lab. Invest. 65:471-478) describes an immediate and early temporal pattern of keratinocyte response to exposure to ultraviolet radiation, but this study was limited to an analysis of the expression patterns of only a few genes. Moreover, no study has successfully provided an analysis of the complete response of the skin and/or the specialized cells of the skin to exposure to ultraviolet radiation. For example, while the study by Abts et al. ((1997) Photochem. Photobio. 66(3):363-367) utilized the methodology of mRNA differential display to study alterations in gene expression mediated by ultraviolet radiation exposure, the study identified only a very small number of ultraviolet radiation-regulated genes due to the difficulty of the technique used.
The role of the ultraviolet-B radiation has been clearly demonstrated in the induction of ultraviolet radiation-induced skin cancers. It has, as a principal chromophore, nucleic acids and, in particular, deoxyribonucleic acid, in which it induces lesions and/or notations (Eller, in Photodamage, pp. 26-56, Blackwell, ed. (1995)). In addition, ultraviolet-B radiation has been linked to premature aging of the skin, characterized by a dry, rough clinical appearance associated with a loss of elasticity, as well as marked wrinkles.
Gene array technology is a powerful, new technique for gene expression monitoring, enabling a global view into changes of expression for an extremely large set of genes. The technology has been applied to the study of many biologic processes (see, e, Lockhart et al. (1966) Nat. Biotechnol. 14:1675-1680; Johnston (1998) Curr. Biol. 8:171-174). For example, the technique has been used in the study of cancer (Scherf et al. (2000) Nat. Genet. 24:236-44; Ross et al. (2000) Nat. Genet. 24:227-35; Welford et al. (1998) Nuc. Acids Res. 26:3059-3065; Alon et al. (1999) Proc. Natl. Acad. Sci. (USA) 96:6745-6750; and Golub et al. (1999) Science 286:531-537); for the study of complex pathways of gene expression (Fambrough et al. (1999) Cell 97:727-741; and Galitski et al. (1999) Science 285:251-254); for the study of the aging process (Cheol-Koo Lee (1999) Science 285:1390-1393; Ly et al. (2000) Science 287:2486-92; Harkin (1999) Cell 97:575-586); and for the study of the stress response of cells to particular damaging agents (Jelinsky et al. (1999) Proc. Natl. Acad. Sci. (USA) 96:1486-1491)).
Pharmacological agents useful in the treatment of photodamaged skin have been identified. For example, the normal repair processes in photodamaged skin have been enhanced pharmacologically. The first to be assessed for this property was Tretinoin (all-trans-retinoic acid). Studies have demonstrated that the reconstruction zone of new collagen was significantly deeper in tretinoin-treated mice, with the enhanced repair being dose and time related. In addition, new collagen was histochemically, ultrastructurally, and biochemically normal. As determined by radioimmunoassay, collagen content was increased two-fold, and mRNAs for types I and III collagen were increased two- to threefold in the tretinoin-treated skin. New collagen synthesis was localized with immunofluorescence techniques in the histologically defined reconstruction zone, and the presence of new elastin and increased fibronectin were also established in the region. Isotretinoin (13-cis-retinoic acid) has also been demonstrated to enhance dermal repair in mice. This repair activity remains retinoid-specific. Fitzpatrick""s Dermatology in Medicine, Fifth Edition, I. M. Freedberg, et al., eds., McGraw-Hill (1999), pp. 1717-1721).
Studies at the molecular level have shown that ultraviolet-B radiation up-regulates the collagen-degrading enzymes collagenase and gelatinase, and that tretinoin reduces the mRNA""s, protein, and activities of these enzymes by 50 to 80 percent. Id. at 1721. Thus, pharmacological agents may be used to reverse skin damage resulting from altered expression of proteins and nucleic acid molecules due to ultraviolet radiation exposure.
Because exposure of specialized cells of the skin to ultraviolet radiation plays an important role in the generation of skin cancer and in the process of premature aging, it would be beneficial to characterize at the molecular level the full response of the skin to exposure to ultraviolet radiation. The present invention provides such information, which was previously lacking in the field. Moreover, epidermal keratinocytes, the main target of environmental ultraviolet radiation, have seldom been used as the model system. The invention described herein redresses this deficiency in the art. Furthermore, nucleic acid molecules and protein molecules in skin cells that are regulated by ultraviolet radiation and the methods provided herein are useful resources for the identification of pharmacological agents for the prevention and treatment of skin cancer and premature aging of the skin.
It has been discovered that certain molecular events occur in the response of a cell to exposure to ultraviolet radiation. More particularly, it has been determined that the expression of a plurality of specific nucleic acid molecules and proteins are regulated in response to ultraviolet radiation exposure. The term xe2x80x9cregulatedxe2x80x9d is used herein to mean that the expression of RNA molecules and/or proteins encoded therein are increased or decreased in response to ultraviolet radiation exposure of a cell relative to the expression levels found in a non-ultraviolet radiation irradiated cell. These ultraviolet radiation-regulated nucleic acid molecules and proteins are further characterized temporally in relation to the cellular response (a first response, a second response, and a third response) and in a quantitative fashion (induced or repressed) in relation to the expression levels found in a cell not exposed to ultraviolet radiation.
These discoveries have been exploited to provide the present invention, which includes compositions of matter, pharmaceutical compositions, methods of identifying a cell exposed to ultraviolet radiation, and screening methods for the identification of compounds that modulate a response by a cell to ultraviolet radiation exposure, the response comprising the altered expression of nucleic acid molecules and/or proteins in the cell.
The cellular responses defined by the present invention relate to the altered expression of RNA molecules and/or protein molecules in a cell exposed to ultraviolet radiation. These responses include the following: (1) a primary first response, a primary second response, and a primary third response, all of which relate to the altered expression of RNA molecules in a cell exposed to ultraviolet radiation; (2) a secondary first response, a secondary second response, and a secondary third response, all of which relate to the altered expression of RNA molecules in a cell exposed to ultraviolet radiation; (3) a tertiary first response, a tertiary second response, and a tertiary third response, all of which relate to the altered expression of proteins in a cell exposed to ultraviolet radiation; and (4) a quaternary first response, a quaternary second response, and a quaternary third response, all of which relate to the altered expression of proteins in a cell exposed to ultraviolet radiation. Thus, the invention provides for a number of groups of RNA molecules or proteins that are regulated in response the exposure of a cell to ultraviolet radiation. These groups include the following: (1) a primary first response group, a primary second response group, and a primary third response group, all of which relate to the altered expression of RNA molecules in a cell exposed to ultraviolet radiation; (2) a secondary first response group, a secondary second response group, and a secondary third response group, all of which relate to the altered expression of RNA molecules in a cell exposed to ultraviolet radiation; (3) a tertiary first response group, a tertiary second response group, and a tertiary third response group, all of which relate to the altered expression of proteins in a cell exposed to ultraviolet radiation; and (4) a quaternary first response group, a quaternary second response group, and a quaternary third response group, all of which relate to the altered expression of proteins in a cell exposed to ultraviolet radiation. The specific differences between these groups are detailed below.
In accordance with a further aspect of the invention, there is provided a composition of matter comprising: (1) a plurality of nucleic acid molecules at least 90% identical to the group of polynucleotides regulated by a cell in response to ultraviolet radiation exposure; and (2) a substrate suitable for binding the nucleic acid molecules of (1). The group of polynucleotides regulated by the cell in response to ultraviolet radiation exposure comprises the following: M20030 Human small proline rich protein (sprII) mRNA, clone 930, X53065, M13903 Human involucrin gene, exon 2, L10343 Human elafin gene, complete cds, M21302 Human small proline rich protein (sprII) mRNA, clone 174N, L05188 H. sapiens small proline-rich protein 2 (SPRR2B) gene, complete cds, Y00787 Human mRNA for MDNCF (monocyte-derived neutrophil chemotactic factor), D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, Alt. Splice, X70326 Macmarcks, X52426 H. sapiens mRNA for cytokeratin 13, S81914 IEX-1=radiation-inducible immediate-early gene [human, placenta, mRNA Partial, 1, M80254 H. sapiens cyclophilin isoform (hCyP3) mRNA, complete cds, L08069 Human heat shock protein, E coli DnaJ homolog mRNA, complete cds, U62800 Human cystatin M (CST6) mRNA, complete cds, L24564 Human Rad mRNA, complete cds, M59465 Human tumor necrosis factor alpha inducible protein A20 mRNA, complete cds, Z49989 H. sapiens mRNA for smoothelin, X57985 H. sapiens genes for histones H2B.1 and H2A, L19779 H. sapiens histone H2A.2 mRNA, complete cds, D42040 Human mRNA for KIAA9001 gene, complete cds, M63573 Human secreted cyclophilin-like protein (SCYLP) mRNA, complete cds, X54489 Human gene for melanoma growth stimulatory activity (MGSA), M92934 Human connective tissue growth factor, complete cds, Z14244 H. sapiens coxVIIb mRNA for cytochrome c oxidase subunit VIIb, M60278 Human heparin-binding EGF-like growth factor mRNA, complete cds, M72885 Human GOS2 gene, 5xe2x80x2 flank and cds, X62083 H. sapiens mRNA for Drosophila female sterile homeotic (FSH) homolog, X67325 H. sapiens p27 mRNA, U04636 Human cyclooxygenase-2 (hCox-2) gene, complete cds, M26311 Human cystic fibrosis antigen mRNA, complete cds, L20688 Human GDP-dissociation inhibitor protein (Ly-GDI) mRNA, complete cds, M27436 Human tissue factor gene, complete cds, with a Alu repetitive sequence in the 3xe2x80x2, AF001294 H. sapiens IPL (IPL) mRNA, complete cds, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, All. Splice, X74874 H. sapiens gene for RNA pol II largest subunit, exon 1, M22919 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Smooth Muscle, Alt. Spli, V00594 Human mRNA for metallothionein from cadmium-treated cells, V00599 Tubulin, Beta, X99920 H. sapiens mRNA for S100 calcium-binding protein A13, M21005 Human migration inhibitory factor-related protein 8 (MRP8) gene, complete cds, U07919 Human aldehyde dehydrogenase 6 mRNA, complete cds, M37583 Human histone (H2A.Z) mRNA, complete cds, S54005 thymosin beta-10 [human, metastatic melanoma cell line, mRNA, 453 nt], D49824 Human HLA-B null allele mRNA, S78771 NAT=CpG island-associated gene [human, mRNA, 1741 nt], M90657 Human tumor antigen (L6) mRNA, complete cds, U09937 Human urokinase-type plasminogen receptor, exon 7, X77794 H. sapiens mRNA for cyclin G1, M28130 Human interleukin 8 (IL8) gene, complete cds, X14850 Human H2AX mRNA encoding histone H2A.X, AB000584 H. sapiens mRNA for TGF-beta superfamily protein, complete cds, U52101 Human YMP mRNA, complete cds, M57731 Human gro-beta mRNA, complete cds, D45248 Human mRNA for proteasome activator hPA28 subunit beta, complete cds, X83416 H. sapiens PrP gene, exon 2, X52882 Human t-complex polypeptide 1 gene, X57351 Human 1-8D gene from interferon-inducible gene family, X53800 Human mRNA for macrophage inflammatory protein-2beta (MIP2beta), Z69043 H. sapiens mRNA translocon-associated protein delta subunit precursor, D38305 Human mRNA for Tob, complete cds, X52979 Human gene for small nuclear ribonucleoproteins SmB and SmBxe2x80x2, S80437 fatty acid synthase {3xe2x80x2 region} [human, breast and HepG2 cells, mRNA Partial, 22, X87679 Major Histocompatibility Complex, Class I, E (Gb:M21533), Z29505 H. sapiens mRNA for nucleic acid binding protein sub2.3, D21853 Human mRNA for KIAA0111 gene, complete cds, X78687 H. sapiens G9 gene encoding sialidase, M13755 Human interferon-induced 17-kD/15-kD protein mRNA, complete cds, M21186 Human neutrophil cytochrome b light chain p22 phagocyte b-cytochrome mRNA, compl, D28235 Human PTGS2 gene for prostaglandin endoperoxide synthase-2, complete cds, M14328 Human alpha enolase mRNA, complete cds, V00599 Tubulin, Beta 2, U90546 Human butyrophilin (BTF4) mRNA, complete cds, K02574, X15729 Human mRNA for nuclear p68 protein, D89052 H. sapiens mRNA for proton-ATPase-like protein, complete cds, M60974 Human growth arrest and DNA-damage-inducible protein (gadd45) mRNA, complete cds, X06956 Tubulin, Alpha 1, Isoform 44, X04654 Human mRNA for U1 RNA-associated 70K protein, M79463 Human PML-2 mRNA, complete CDS, L76568 H. sapiens excision and cross link repair protein (ERCC4) gene, complete genome, Y09022 H. sapiens mRNA for Not56-like protein, X57579 H. sapiens activin beta-A subunit (exon 2), U37690 Human RNA polymerase II subunit (hsRPB10) mRNA, complete cds, X61123 Human BTG1 mRNA, J04456 Human 14 kD lectin mRNA, complete cds, Z49254 H. sapiens L23-related mRNA, U70660 Human copper transport protein HAH1 (HAH1) mRNA, complete cds, D86974 Human mRNA for KIAA0220 gene, partial cds, Y07604 H. sapiens mRNA for nucleoside-diphosphate kinase, AF006084 H. sapiens Arp2/3 protein complex subunit p41-Arc (ARC41) mRNA, complete cds, Y00503 Human mRNA for keratin 19, L26336 Heat Shock Protein, 70 KD (Gb:Y00371), M62831 Human transcription factor ETR101 mRNA, complete cds, Z22548 H. sapiens thiol-specific antioxidant protein mRNA, U40369 Human spermidine/spermine N1-acetyltransferase (SSAT) gene, complete cds, M12125 Human fibroblast muscle-type tropomyosin mRNA, complete cds, X51345 Human jun-B mRNA for JUN-B protein, Z21507 H. sapiens EF-1delta gene encoding human elongation factor-1-delta, U20734 Human transcription factor junB (junB) gene, 5xe2x80x2 region and complete cds, D13413 Human mRNA for tumor-associated 120 kD nuclear protein p120, partial cds(carbox, LA2379 H. sapiens bone-derived growth factor (BPGF-1) mRNA, complete cds, X15822 Human COX VIIa-L mRNA for liver-specific cytochrome c oxidase (EC 1.9.3.1.), D86988 Human mRNA for KIAA0221 gene, complete cds, M26730 Human mitochondrial ubiquinone-binding protein (QP) gene, exon 4, M69043 H. sapiens MAD-3 mRNA encoding IkB-like activity, complete cds, D38251 Human mRNA for RPB5 (XAP4), complete cds, M30703 Human amphiregulin (AR) gene, exon 6, clones lambda-ARH(6,12), L76200 Human guanylate kinase (GUK1) mRNA, complete cds, M34516 Human omega light chain protein 14.1 (Ig lambda chain related) gene, exon 3, U26727 Human p16INK4/MTS1 mRNA, complete cds, U53830 H. sapiens interferon regulatory factor 7A mRNA, complete cds, M22960 Human protective protein mRNA, complete cds, D89667 H. sapiens mRNA for c-myc binding protein, complete cds, L16862 H. sapiens G protein-coupled receptor kinase (GRK6) mRNA, complete cds, M19309 Human slow skeletal muscle troponin T mRNA, clone H22h, D64142 Human mRNA for histone H1x, complete cds, U41515 Human deleted in split hand/split foot 1 (DSS1) mRNA, complete cds, J04611 Human lupus p70 (Ku) autoantigen protein mRNA, complete cds, U35048 Human TSC-22 protein mRNA, complete cds, X82693 H. sapiens mRNA for E48 antigen, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, U72649 Human BTG2 (BTG2) mRNA, complete ed, X92896 H. sapiens mRNA for ITBA2 protein, X74104 H. sapiens mRNA for TRAP beta subunit, M84332 Human ADP-ribosylation factor 1 gene, exons 2-5, D15050 Human mRNA for transcription factor AREB6, complete cds, D10923 Human mRNA for HM74, M84739 Human autoantigen calreticulin mRNA, complete cds, U09813 Human mitochondrial ATP synthase subunit 9, P3 gene copy, mRNA, nuclear gene enc, X67951 H. sapiens mRNA for proliferation-associated gene (pag), X82200 H. sapiens Staf50 mRNA, L27706 Human chaperonin protein (Tcp20) gene complete cds, U69126 Human FUSE binding protein 2 (FBP2) mRNA, partial cds, M12529 Human apolipoprotein E mRNA, complete cds, X71129 H. sapiens mRNA for electron transfer flavoprotein beta subunit, U28386 Human nuclear localization sequence receptor hSRP1alpha mRNA, complete cds, U41766 Human metalloprotease/disintegrin/cysteine-rich protein precursor (MDC9) mRNA, c, AF006041 H. sapiens Fas-binding protein (DAXX) mRNA, partial cds, U28749 Human high-mobility group phosphoprotein isoform I-C (HMGIC) mRNA, complete cds, M60483 Human protein phosphatase 2A catalytic subunit-alpha gene, complete cds, U07664 Human HB9 homeobox gene, exons 2 and 3 and complete cds, U13991 Human TATA-binding protein associated factor 30 kD subunit (taffII30) mRNA, comp, J04794 Human aldehyde reductase mRNA, complete cds, U51586 Human siah binding protein 1 (SiahBP1) mRNA, partial cds, M58026 Human NB-1 mRNA, complete cds, X52425 Human IL4R mRNA for the interleukin 4 receptor, X94563 H. sapiens dbi/acbp gene exon 1 and 2, X68277 H. sapiens CL 100 mRNA for protein tyrosine phosphatase, X56681 Human junD mRNA, V01512 Human cellular oncogene c-fos (complete sequence), U09578 H. sapiens MAPKAP kinase (3 pK) mRNA, complete cds, L13391 Human helix-loop-helix basic phosphoprotein (GOS8) gene, complete cds, U62317 Chromosome 22q13 BAC Clone C11987SK-384D8 complete sequence, M16364 Human creatine kinase-B mRNA, complete cds, L19437 Human transaldolase mRNA containing transposable element, complete cds, X53416 Human mRNA for actin-binding protein (filamin) (ABP-280), X52560 Nuclear Factor Nf-I16, X78549 H. sapiens brk mRNA for tyrosine kinase, L11066 Human mRNA sequence, X74008 H. sapiens mRNA for protein phosphatase 1 gamma, X87241 H. sapiens mRNA for hFat protein, S68616 Na+H+ exchanger NHE-1 isoform [human, heart, mRNA, 4516 nt], D13705 Human mRNA for fatty acids omega-hydroxylase (cytochrome P-450HKV), complete cds, D86966 Human mRNA for KIAA0211 gene, complete cds, U17327 Human neuronal nitric oxide synthase (NOS1) mRNA, complete cds, U89336 Human HLA class III region containing NOTCH4 gene, partial sequence, homeobox PB, D85527 H. sapiens mRNA for LIM domain, partial cds, L07517 Mucin 6, Gastric (Gb:L07517), M58459 Human ribosomal protein (RPS4Y) isoform mRNA, complete cds, U65579 Human mitochondrial NADH dehydrogenase-ubiquinone Fexe2x80x94S protein 8, 23 kD subunit, M19961 Human cytochrome c oxidase subunit Vb (coxVb) mRNA, complete cds, M29064 Human hnRNP B1 protein mRNA, X64330 H. sapiens mRNA for ATP-citrate lyase, X89267 H. sapiens DNA for uroporphyrinogen decarboxylase gene, X91247 H. sapiens mRNA for thioredoxin reductase, L11672 Human Kruppel related zinc finger protein (HTF10) mRNA, complete cds, X78992 H. sapiens ERF-2 mRNA, L19314 Human HRY gene, complete cds, D90086 Human pyruvate dehydrogenase (EC 1.2.4.1) beta subunit gene, exons 1-10, X12794 Human v-erbA related ear-2 gene, L22005 Human ubiquitin conjugating enzyme mRNA, partial cds, U01337 Human Ser/Thr protein kinase (A-RAF-1) gene, complete cds, M34182 Human testis-specific protein kinase gamma-subunit mRNA, complete cds, L08246 Human myeloid cell differentiation protein (MCL1) mRNA, L37042 H. sapiens casein kinase I alpha isoform (CSNK1A1) mRNA, complete cds, L04731 H. sapiens translocation T(4:11) of ALL-1 gene to chromosome 4, D87071 Human mRNA for KIAA0233 gene, complete cds, S74017 Nrf2=NF-E2-like basic leucine zipper transcriptional activator [human, hemin-ind, L41351 H. sapiens prostasin mRNA, complete cds, L00352 Human low density lipoprotein receptor gene, exon 18, D50683 H. sapiens mRNA for TGF-betaIIR alpha, complete cds, X89750 H. sapiens mRNA for TGIF protein, D13988 Human rab GDI mRNA, complete cds, M12886 Human T-cell receptor active beta-chain mRNA, complete cds, M55265 Human casein kinase II alpha subunit mRNA, complete cds, J03161 Human serum response factor (SRF) mRNA, complete cds, M58286 H. sapiens tumor necrosis factor receptor mRNA, complete cds, U88629 Human RNA polymerase II elongation factor ELL2, complete cds, X04412 Human mRNA for plasma gelsolin, L27943 H. sapiens cytidine deaminase (CDA) mRNA, complete cds, U90716 Human cell surface protein HCAR mRNA, complete cds, M24547 Amyloid Beta (A4) Precursor Protein, Alt. Splice 2, A4(751), U05875 Human clone pSK1 interferon gamma receptor accessory factor-1 (AF-1) mRNA, compl, Z11585 Potassium Channel Protein (Gb:Z11585), M58603 Human nuclear factor kappa-B DNA binding subunit (NF-kappa-B) mRNA, complete cds, D87442 Human mRNA for KIAA0253 gene, partial cds, M76482 Human 130-kD pemphigus vulgaris antigen mRNA, complete cds, U56418 Human lysophosphatidic acid acyltransferase-beta mRNA, complete cds, J00120 Proto-Oncogene C-Myc, Alt. Splice 3, Orf 114, U68142 Human RalGDS-like 2 (RGL2) mRNA, partial cds, U88898 Human endogenous retroviral H protease/integrase-derived ORF1 mRNA, complete cds, M91083 Human DNA-binding protein (HRC1) mRNA, complete cds, Z30643 H. sapiens mRNA for chloride channel (putative) 2139 bp, X12953 Human rab2 mRNA, YPT1-related and member of ras family, D78129 H. sapiens mRNA for squalene epoxidase, partial cds, U63825 Human hepatitis delta antigen interacting protein A (dipA) mRNA, complete cds, S78825 Id1, M54915 Human h-pim-1 protein (h-pim-1) mRNA, complete cds, X04828 Human mRNA for G(i) protein alpha-subunit (adenylate cyclase inhibiting GTP-bind, X06323 Human MRL3 mRNA for ribosomal protein 13 homolog (MRL3=mammalian ribosome L, D14043 Human mRNA for MGC-24, complete cds, L38951 H. sapiens importin beta subunit mRNA, complete cds, U34252 Human gamma-aminobutyraldehyde dehydrogenase mRNA, complete cds, M13829 Human putative raf related protein (pks/a-raf) mRNA, partial cds, U33821 Human tax1-binding protein TXBP151 mRNA, complete cds, U66616 Human SWI/SNF complex 170 KD subunit (BAF170) mRNA, complete cds, U29607 Human methionine aminopeptidase mRNA, complete cds, D14520 Human mRNA for GC-Box binding protein BTEB2, complete cds, D14874 H. sapiens mRNA for adrenomedullin precursor, complete cds, D85429 H. sapiens gene for heat shock protein 40, complete cds, M69181 Human nonmuscle myosin heavy chain-B (MYH10) mRNA, partial cds, U60205 Human methyl sterol oxidase (ERG25) mRNA, complete cds, X75342 H. sapiens SHB mRNA, D45906 H. sapiens mRNA for LIMK-2, complete cds, X59434 Human rohu mRNA for rhodanese, M96803 Human general beta-spectrin (SPTBN1) mRNA, complete cds, D79994 Human mRNA for KIAA0172 gene, partial cds, D86965 Human mRNA for KIAA0210 gene, complete cds, Y13647 Stearoyl-Coenzymea Desaturase, X52541 Human mRNA for early growth response protein 1 (hEGR1), Z26317 H. sapiens mRNA for desmoglein 2, M57763 Human ADP-ribosylation factor (hARF6) mRNA, complete cds, L38490 H. sapiens ADP-ribosylation factor mRNA, complete cds, D87438 Human mRNA for KIAA0251 gene, partial cds, M31627 Human X box binding protein-1 (XBP-1) mRNA, complete cds, X80692 H. sapiens ERK3 mRNA, U37122 Human adducin gamma subunit mRNA, complete cds, M83667 Human NF-IL6-beta protein mRNA, complete cds, J05211 Desmoplakin I, D42123 H. sapiens mRNA for ESP1/CRP2, complete cds, X90858 H. sapiens mRNA for uridine phosphorylase, X76717 H. sapiens MT-11 mRNA, Y08915 H. sapiens mRNA for alpha 4 protein, U30999 Human (memc) mRNA, 3xe2x80x2UTR, L77886 Human protein tyrosine phosphatase mRNA, complete cds, U14603 Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, U28480 Uncoupling Protein Ucp, X53586 Human mRNA for integrin alpha 6, M64347 Human novel growth factor receptor mRNA, 3xe2x80x2 cds, U52100 Human XMP mRNA, complete cds, D21852 Human mRNA for KIAA0029 gene, partial cds, X05409 Human RNA for mitochondrial aldehyde dehydrogenase I ALDH I (EC 1.2.1.3), D87462 Human mRNA for KIAA0272 gene, partial cds, L40391 H. sapiens (clone s153) mRNA fragment, D87469 Human mRNA for KIAA0279 gene, partial cds, S73591 brain-expressed HHCPA78 homolog [human, HL60 acute promyelocytic leukemia cells, L19267 H. sapiens 59 protein mRNA, 3xe2x80x2 end, M81601 Human transcription elongation factor (SII) mRNA, complete cds, X52611 Human mRNA for transcription factor AP-2, U28811 Human cysteine-rich fibroblast growth factor receptor (CFR-1) mRNA, complete cds, L31801 H. sapiens monocarboxylate transporter 1 (SLC16A1) mRNA, complete cds, M13929 Human c-myc-P64 mRNA, initiating from promoter P0, (HLmyc2.5) partial cds, L48546 H. sapiens tuberin (TSC2) gene, exons 38, 39, 40 and 41, L00058 Human (GH) germline c-myc proto-oncogene, exon 3 and 3xe2x80x2 flank, U09587 Human glycyl-tRNA synthetase mRNA, complete cds, L37127 H. sapiens RNA polymerase II mRNA, complete cds, U52426 H. sapiens GOK (STIM1) mRNA, complete cds, U72066 H. sapiens CtBP interacting protein CtIP (CtIP) mRNA, complete cds, U83115 Human non-lens beta gamma-crystallin like protein (AIM1) mRNA, partial cds, M90656 Human gamma-glutamylcysteine synthetase (GCS) mRNA, complete cds, D90209 Human mRNA for DNA binding protein TAXREB67, D83777 Human mRNA for KIAA0193 gene, complete cds, U42031 Human 54 kD progesterone receptor-associated immunophilin FKBP54 mRNA, partial, M80244 Human E16 mRNA, complete cds, D31883 Human mRNA for KIAA0059 gene, complete cds, J04444 Human cytochrome c-1 gene, complete cds, M38258 Human retinoic acid receptor gamma 1 mRNA, complete cds, M95787 Human 22 kD smooth muscle protein (SM22) mRNA, complete cds, U00968 Human SREBP-1 mRNA, complete cds, K03195 Human (HepG2) glucose transporter gene mRNA, complete cds, X92720 H. sapiens mRNA for phosphoenolpyruvate carboxykinase, X77366 H. sapiens HBZ17 mRNA, U53347 Human neutral amino acid transporter B mRNA, complete cds, X80695 H. sapiens OXA1Hs mRNA, J04102 Human erythroblastosis virus oncogene homolog 2 (ets-2) mRNA, complete eds, S75762 Oncogene Tls/Chop, Fusion Activated, U14550 Human sialyltransferase SThM (sthm) mRNA, complete cds, L09229 Human long-chain acyl-coenzyme A synthetase (FACL1) mRNA, complete cds, X76534 H. sapiens NMB mRNA, M55268 Human casein kinase II alphaxe2x80x2 subunit mRNA, complete cds, M27396 Human asparagine synthetase mRNA, complete cds, U37519 Human aldehyde dehydrogenase (ALDH8) mRNA, complete cds, X69111 H. sapiens HLH 1R21 mRNA for helix-loop-helix protein, M77836 Human pyrroline 5-carboxylate reductase mRNA, complete cds, D32050 Human mRNA for alanyl-tRNA synthetase, complete cds, X01630 Human mRNA for argininosuccinate synthetase. This group of ultraviolet radiation-regulated polynucleotides is hereinafter referred to as the xe2x80x9ccomplete response groupxe2x80x9d of ultraviolet radiation-regulated polynucleotides.
In accordance with a further aspect of the invention, there is provided a composition of matter comprising: (1) a plurality of nucleic acid molecules at least 90% identical to the group of polynucleotides regulated by a cell in response to ultraviolet radiation exposure; and (2) a substrate suitable for binding the nucleic acid molecules of (1). The group of polynucleotides regulated by the cell in response to ultraviolet radiation exposure comprises the following: M20030 Human small proline rich protein (sprII) mRNA, clone 930, X53065, M13903 Human involucrin gene, exon 2, L10343 Human elafin gene, complete cds, M21302 Human small proline a rich protein (sprII) mRNA, clone 174N, L05188 H. sapiens small proline-rich protein 2 (SPRR2B) gene, complete cds, Y00787 Human mRNA for MDNCF (monocyte-derived neutrophil chemotactic factor), D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, Alt. Splice, X70326 Macmarcks, X52426 H. sapiens mRNA for cytokeratin 13, S81914 IEX-1=radiation-inducible immediate-early gene [human, placenta, mRNA Partial, 1, M80254 H. sapiens cyclophilin isoform (hCyP3) mRNA, complete cds, L08069 Human heat shock protein, E. coli DnaJ homolog mRNA, complete cds, U62800 Human cystatin M (CST6) mRNA, complete cds, L24564 Human Rad mRNA, complete cds, M59465 Human tumor necrosis factor alpha inducible protein A20 mRNA, complete cds, Z49989 H. sapiens mRNA for smoothelin, X57985 H. sapiens genes for histones H2B.1 and H2A, L19779 H. sapiens histone H2A.2 mRNA, complete cds, D42040 Human mRNA for KIAA9001 gene, complete cds, M63573 Human secreted cyclophilin-like protein (SCYLP) mRNA, complete cds, X54489 Human gene for melanoma growth stimulatory activity (MGSA), M92934 Human connective tissue growth factor, complete cds, Z14244 H. sapiens coxVIIb mRNA for cytochrome c oxidase subunit VIIb, M60278 Human heparin-binding EGF-like growth factor mRNA, complete cds, M72885 Human GOS2 gene, 5xe2x80x2 flank and cds, X62083 H. sapiens mRNA for Drosophila female sterile homeotic (FSH) homolog, X67325 H. sapiens p27 mRNA, U04636 Human cyclooxygenase-2 (hCox-2) gene, complete cds, M26311 Human cystic fibrosis antigen mRNA, complete cds, L20688 Human GDP-dissociation inhibitor protein (Ly-GDI) mRNA, complete cds, M27436 Human tissue factor gene, complete cds, with a Alu repetitive sequence in the 3xe2x80x2, AF001294 H. sapiens IPL (IPL) mRNA, complete cds, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, Alt. Splice. X74874 H. sapiens gene for RNA pol II largest subunit, exon 1, M22919,Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Smooth Muscle, Alt. Spli, V00594 Human mRNA for metallothionein from cadmium-treated cells, V00599 Tubulin, Beta, X99920 H. sapiens mRNA for S100 calcium-binding protein A13, M21005 Human migration inhibitory factor-related protein 8 (MRP8) gene, complete cds, U07919 Human aldehyde dehydrogenase 6 mRNA, complete cds, M37583 Human histone (H2A.Z) mRNA, complete cds, S54005 thymosin beta-10 [human, metastatic melanoma cell line, mRNA, 453 nt], D49824 Human HLA-B null allele mRNA, S78771 NAT=CpG island-associated gene [human, mRNA, 1741 nt], M90657 Human tumor antigen (L6) mRNA, complete cds, U09937 Human urokinase-type plasminogen receptor, exon 7, X77794 H. sapiens mRNA for cyclin G1, M28130 Human interleukin 8 (IL8) gene, complete cds, X14850 Human H2A.X mRNA encoding histone H2A.X, AB000584 H. sapiens mRNA for TGF-beta superfamily protein, complete cds, U52101 Human YMP mRNA, complete cds, M57731 Human gro-beta mRNA, complete cds, D45248 Human mRNA for proteasome activator hPA28 subunit beta, complete cds, X83416 H. sapiens PrP gene, exon 2, X52882 Human t-complex polypeptide 1 gene, X57351 Human 1-8D gene from interferon-inducible gene family, X53800 Human mRNA for macrophage inflammatory protein-2beta (MIP2beta), Z69043 H. sapiens mRNA translocon-associated protein delta subunit precursor, D38305 Human mRNA for Tob, complete cds, t X52979 Human gene for small nuclear ribonucleoproteins SmB and SmBxe2x80x2, S80437 fatty acid synthase {3xe2x80x2 region} (human, breast and HepG2 cells, mRNA Partial, 22, X87679 Major Histocompatibility Complex, Class I, E (Gb:M21533), Z29505 H. sapiens mRNA for nucleic acid binding protein sub2.3, D21853 Human mRNA for KIAA0111 gene, complete cds, X78687 H. sapiens G9 gene encoding sialidase, M13755 Human interferon-induced 17-kD/15-kD protein mRNA, complete cds, M21186 Human neutrophil cytochrome b light chain p22 phagocyte b-cytochrome mRNA, compl, 8235_s_at D28235 Human PTGS2 gene for prostaglandin endoperoxide synthase-2, complete cds, M14328 Human alpha enolase mRNA, complete cds, V00599 Tubulin, Beta 2, U90546 Human butyrophilin (BTF4) mRNA, complete cds, K02574, X15729 Human mRNA for nuclear p68 protein, D89052 H. sapiens mRNA for proton-ATPase-like protein, complete cds, M60974 Human growth arrest and DNA-damage-inducible protein (gadd45) mRNA, complete cds, X06956 Tubulin, Alpha 1, Isoform 44, X04654 Human mRNA for U1 RNA-associated 70K protein, M79463 Human PML-2 mRNA, complete CDS, L76568 H. sapiens excision and cross link repair protein (ERCC4) gene, complete genom, Y09022 H. sapiens mRNA for Not56-like protein, X57579 H. sapiens activin beta-A subunit (exon 2), 37690 Human RNA polymerase II subunit (hsRPB10) mRNA, complete cds, X61123 Human BTG1 mRNA, J04456 Human 14 kD lectin mRNA, complete cds, Z49254 H. sapiens L23-related mRNA, U70660 Human copper transport protein HAH1 (HAH1) mRNA, complete cds, D86974 Human mRNA for KIAA0220 gene, partial cds, AF006084 H. sapiens Arp2/3 protein complex subunit p41-Arc (ARC41) mRNA, complete cds, Y00503 Human mRNA for keratin 19, M62831 Human transcription factor ETR101 mRNA, complete cos, Z22548 H. sapiens thiol-specific antioxidant protein mRNA, U40369 Human spermidine/spermine N1-acetyltransferase (SSAT) gene, complete cds, M12125 Human fibroblast muscle-type tropomyosin mRNA, complete cds, X51345 Human jun-B mRNA for JUN-B protein, Z21507 H. sapiens EF-1delta gene encoding human elongation factor-1-delta, U20734 Human transcription factor junB (junB) gene, 5xe2x80x2 region and complete cds, D13413 Human mRNA for tumor-associated 120 kD nuclear protein p120, partial cds(carbox, L42379 H. sapiens bone-derived growth factor (BPGF-1) mRNA, complete cds, X15822 Human COX VIIa-L mRNA for liver-specific cytochrome c oxidase (EC 1.9.3.1.), D86988 Human mRNA for KIAA0221 gene, complete cds, M26730 Human mitochondrial ubiquinone-binding protein (QP) gene, exon 4, M69043 H. sapiens MAD-3 mRNA encoding IkB-like activity, complete cds, D38251 Human mRNA for RPB5 (XAP4), complete cds, L76200 Human guanylate kinase (GUK1) mRNA, complete cds, M34516 Human omega light chain protein 14.1 (Ig lambda chain related) gene, exon 3, U26727 Human p16INK4/MTS1 mRNA, complete cds, U53830 H. sapiens interferon regulatory factor 7A mRNA, complete cds, M22960 Human protective protein mRNA, complete cds, D89667 H. sapiens mRNA for c-myc binding protein, complete cds, M19309 Human slow skeletal muscle troponin T mRNA, clone H22h, D64142 Human mRNA for histone H1x, complete cds, U41515 Human deleted in split hand/split foot 1 (DSS1) mRNA, complete cds, J04611 Human lupus p70 (Ku) autoantigen protein mRNA, complete cds, U35048 Human TSC-22 protein mRNA, complete cds, X82693 H. sapiens mRNA for E48 antigen, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, U72649 Human BTG2 (BTG2) mRNA, complete cds, X92896 H. sapiens mRNA for ITBA2 protein, D10923 Human mRNA for HM74, M84739 Human autoantigen calreticulin mRNA, complete eds, U09813 Human mitochondrial ATP synthase subunit 9, P3 gene copy, mRNA, nuclear gene enc, X67951 H. sapiens mRNA for proliferation-associated gene (pag), L27706 Human chaperonin protein (Tcp20) gene complete cds, U69126 Human FUSE binding protein 2 (FBP2) mRNA, partial eds, M12529 Human apolipoprotein E mRNA, complete cds, X71129 H. sapiens mRNA for electron transfer flavoprotein beta subunit, U13991 Human TATA-binding protein associated factor 30 kD subunit (tafII30) mRNA, comp, J04794 Human aldehyde reductase mRNA, complete cds, U51586 Human siah binding protein 1 (SiahBP1) mRNA, partial cds, M58026 Human NB-1 mRNA, complete cds, X68277 H. sapiens CL 100 mRNA for protein tyrosine phosphatase, X56681 Human junD mRNA, V01512 Human cellular oncogene c-fos (complete sequence), U09578 H. sapiens MAPKAP kinase (3 pK) mRNA, complete cds, L13391 Human helix-loop-helix basic phosphoprotein (G0S8) gene, complete cds, U62317 Chromosome 22q13 BAC Clone CIT987SK-384D8 complete sequence, M16364 Human creatine kinase-B mRNA, complete cds, L19437 Human transaldolase mRNA containing transposable element, complete cds, X53416 Human mRNA for actin-binding protein (filamin) (ABP-280), X52560 Nuclear Factor Nf-I16, M58459 Human ribosomal protein (RPS4Y) isoform mRNA, complete cds, U65579 Human mitochondrial NADH dehydrogenase-ubiquinone Fexe2x80x94S protein 8, 23 kD subunit, M19961 Human cytochrome c oxidase subunit Vb (coxVb) mRNA, complete cds, M29064 Human hnRNP B1 protein mRNA, D90086 Human pyruvate dehydrogenase (EC 1.2.4.1) beta subunit gene, exons 1-10, L04731 H. sapiens translocation T(4:11) of ALL-1 gene to chromosome 4, D87071 Human mRNA for KIAA0233 gene, complete cds, X04412 Human mRNA for plasma gelsolin, L27943 H. sapiens cytidine deaminase (CDA) mRNA, complete cds, U68142 Human RalGDS-like 2 (RGL2) mRNA, partial cds, U63825 Human hepatitis delta antigen interacting protein A (dipA) mRNA, complete cds, X04828 Human mRNA for G(i) protein alpha-subunit (adenylate cyclase inhibiting GTP-bind, L38951 H. sapiens importin beta subunit mRNA, complete cds, M31627 Human X box binding protein-1 (XBP-1) mRNA, complete cds, J04444 Human cytochrome c-1 gene, complete cds, S75762 Oncogene Tls/Chop, Fusion Activated. This group of ultraviolet radiation-regulated polynucleotides is hereinafter referred to as the xe2x80x9cinduced response groupxe2x80x9d of ultraviolet radiation-regulated polynucleotides.
In accordance with a further aspect of the invention, there is provided a composition of matter comprising: (1) a plurality of nucleic acid molecules at least 90% identical to the group of polynucleotides regulated by a cell in response to ultraviolet radiation exposure; and (2) a substrate suitable for binding the nucleic acid molecules of (1). The group of polynucleotides regulated by the cell in response to ultraviolet radiation exposure comprises the following: D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, L08069 Human heat shock protein, E. coli DnaJ homolog mRNA, complete cds, X77794 H. sapiens mRNA for cyclin G1, D89052 H. sapiens mRNA for proton-ATPase-like protein, complete cds, L26336 Heat Shock Protein, 70 KD (Gb:Y00371), M30703 Human amphiregulin (AR) gene, exon 6, clones lambda-ARH(6,12), L16862 H. sapiens G protein-coupled receptor kinase (GRK6) mRNA, complete cds, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, U72649 Human BTG2 (BTG2) mRNA, complete cds, X74104 H. sapiens mRNA for TRAP beta subunit, M84332 Human ADP-ribosylation factor 1 gene, exons 2-5, D15050 Human mRNA for transcription factor AREB6, complete cds, U28386 Human nuclear localization sequence receptor hSRP1alpha mRNA, complete cds, U41766 Human metalloprotease/disintegrin/cysteine-rich protein precursor (MDC9) mRNA, c, AF006041 H. sapiens Fas-binding protein (DAXX) mRNA, partial cds, U28749 Human high-mobility group phosphoprotein isoform I-C (HMGIC) mRNA, complete cds, M60483 Human protein phosphatase 2A catalytic subunit-alpha gene, complete cds, U07664 Human HB9 homeobox gene, exons 2 and 3 and complete cds, X52425 Human IL-4-R mRNA for the interleukin 4 receptor, X94563 H. sapiens dbi/acbp gene exon 1 and 2, L11066 Human mRNA sequence, X74008 H. sapiens mRNA for protein phosphatase 1 gamma, X87241 H. sapiens mRNA for hFat protein, S68616 Na+/H+ exchanger NHE-1 isoform [human, heart, mRNA, 4516 nt], D13705 Human mRNA for fatty acids omega-hydroxylase (cytochrome P450HKV), complete cds, D86966 Human mRNA for KIAA0211 gene, complete cds, U17327 Human neuronal nitric oxide synthase (NOS1) mRNA, complete cds, U89336 Human HLA class III region containing NOTCH4 gene, partial sequence, homeobox PB, D85527 H. sapiens mRNA for LIM domain, partial cds, L07517 Mucin 6, Gastric (Gb:L07517), X64330 H. sapiens mRNA for ATP-citrate Iyase, X89267 H. sapiens DNA for uroporphyrinogen decarboxylase gene, X91247 H. sapiens mRNA for thioredoxin reductase, L11672 Human Kruppel related zinc finger protein (HTF10) mRNA, complete cds, X78992 H. sapiens ERF-2 mRNA, L19314 Human HRY gene, complete cds, X12794 Human v-erbA related ear-2 gene, L22005 Human ubiquitin conjugating enzyme mRNA, partial cds, U01337 Human Ser/Thr protein kinase (A-RAF-1) gene, complete cds, M34182 Human testis-specific protein kinase gamma-subunit mRNA, complete cds, L08246 Human myeloid cell differentiation protein (MCL1) mRNA, L37042 H. sapiens casein kinase I alpha isoform (CSNK1A1) mRNA, complete cds, D87071 Human mRNA for KIAA0233 gene, complete cds, S74017 Nrf2=NF-E2-like basic leucine zipper transcriptional activator [human, hemin-ind, L41351 H. sapiens prostasin mRNA, complete cds, L00352 Human low density lipoprotein receptor gene, exon 18, D50683 H. sapiens mRNA for TGF-betaIIR alpha, complete cds, X89750 H. sapiens mRNA for TGIF protein, t D13988 Human rab GDI mRNA, complete cds, M12886 Human T-cell receptor active beta-chain mRNA, complete cds, M55265 Human casein kinase II alpha subunit mRNA, complete cds, J03161 Human serum response factor (SRF) mRNA, complete cds, M58286 H. sapiens tumor necrosis factor receptor mRNA, complete cds, U88629 Human RNA polymerase II elongation factor ELL2, complete cds, U90716 Human cell surface protein HCAR mRNA, complete cds, M24547 Amyloid Beta (A4) Precursor Protein, Alt. Splice 2, A4(751), U05875 Human clone pSK1 interferon gamma receptor accessory factor-1 (AF-1) mRNA, compl, M58603 Human nuclear factor kappa-B DNA binding subunit (NF-kappa-B) mRNA, complete cds, D87442 Human mRNA for KIAA0253 gene, partial cds, M76482 Human 130-kD pemphigus vulgaris antigen mRNA, complete cds, U56418 Human lysophosphatidic acid acyltransferase-beta mRNA, complete cds, J00120 Proto-Oncogene C-Myc, Alt. Splice 3, Orf 114, U88898 Human endogenous retroviral H protease/integrase-derived ORF1 mRNA, complete cds, M91083 Human DNA-binding protein (HRC1) mRNA, complete cds, Z30643 H. sapiens mRNA for chloride channel (putative) 2139 bp, X12953 Human rab2 mRNA, YPT1-related and member of ras family, D78129 H. sapiens mRNA for squalene epoxidase, partial cds, S78825 Id1, M54915 Human h-pim-1 protein (h-pim-1) mRNA, complete cds, X06323 Human MRL3 mRNA for ribosomal protein U3 homolog (MRL3=mammalian ribosome L, D14043 Human mRNA for MGC-24, complete cds, U34252 Human gamma-aminobutyraldehyde dehydrogenase mRNA, complete cds, M13829 Human putative raf related protein (pks/a-raf) mRNA, partial cds, U33821 Human tax1-binding protein TXBP151 mRNA, complete cds, U66616 Human SWI/SNF complex 170 KD subunit (BAF170) mRNA, complete cds, U29607 Human methionine aminopeptidase mRNA, complete cds, D14520 Human mRNA for GC-Box binding protein BTEB2, complete cds, D14874 H. sapiens mRNA for adrenomedullin precursor, complete cds, D85429 H. sapiens gene for heat shock protein 40, complete cds, t M69181 Human nonmuscle myosin heavy chain-B (MYH10) mRNA, partial cds, U60205 Human methyl sterol oxidase (ERG25) mRNA, complete cds, X75342 H. sapiens SHB mRNA, t D45906 H. sapiens mRNA for LIMK-2, complete cds, X59434 Human rohu mRNA for rhodanese, M96803 Human general beta-spectrin (SFMBN1) mRNA, complete cds, D79994 Human mRNA for KIAA0172 gene, partial cds, D86965 Human mRNA for KIAA0210 gene, complete cds, Y13647 Stearoyl-Coenzymea Desaturase, X52541 Human mRNA for early growth response protein 1 (hEGR1), Z26317 H. sapiens mRNA for desmoglein 2, t M57763 Human ADP-ribosylation factor (hARF6) mRNA, complete cds, L38490 H. sapiens ADP-ribosylation factor mRNA, complete cds, D87438 Human mRNA for KIAA0251 gene, partial cds, M31627 Human X box binding protein-1 (XBP-1) mRNA, complete cds, X80692 H. sapiens ERK3 mRNA, U37122 Human adducin gamma subunit mRNA, complete cds, M83667 Human NF-IL-6beta protein mRNA, complete cds, J05211 Desmoplakin I, D42123 H. sapiens mRNA for ESP1/CRP2, complete cds, X90858 H. sapiens mRNA for uridine phosphorylase, X76717 H. sapiens MT-11 mRNA, Y08915 H. sapiens mRNA for alpha 4 protein, U30999 Human (memc) mRNA, 3xe2x80x2UTR, L77886 Human protein tyrosine phosphatase mRNA, complete cds, U14603 Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, U28480 Uncoupling Protein Ucp, X53586 Human mRNA for integrin alpha 6, M64347 Human novel growth factor receptor mRNA, 3xe2x80x2 cds, U52100 Human XMP mRNA, complete cds, D21852 Human mRNA for KIAA0029 gene, partial cds. X05409 Human RNA for mitochondrial aldehyde dehydrogenase I ALDH I (EC 1.2.1.3), D87462 Human mRNA for KIAA0272 gene, partial cds, L40391 H. sapiens (clone s153) mRNA fragment, D87469 Human mRNA for KIAA0279 gene, partial cds, S73591 brain-expressed HHCPA78 homolog [human, HL-60 acute promyelocytic leukemia cells, L19267 H. sapiens 59 protein mRNA, 3xe2x80x2 end, M81601 Human transcription elongation factor (SIT) mRNA, complete cds, X52611 Human mRNA for transcription factor AP-2, U28811 Human cysteine-rich fibroblast growth factor receptor (CFR-1) mRNA, complete cds, L31801 H. sapiens monocarboxylate transporter 1 (SLC16A1) mRNA, complete cds, M13929 Human c-myc-P64 mRNA, initiating from promoter P0, (HLmyc2.5) partial cds, L48546 H. sapiens tuberin (TSC2) gene, exons 38, 39, 40 and 41, L00058 Human (GH) germline c-myc proto-oncogene, exon 3 and 3xe2x80x2 flank, U09587 Human glycyl-tRNA synthetase mRNA, complete cds, L37127 H. sapiens RNA polymerase II mRNA, complete cds, U52426 H. sapiens GOK (STIM1) mRNA, complete cds, U72066 H. sapiens CtBP interacting protein CtIP (CtIP) mRNA, complete cds, U83115 Human nonlens beta gamma-crystallin like protein (AIM1) mRNA, partial cds, M90656 Human gamma-glutamylcysteine synthetase (GCS) mRNA, complete cds, D90209 Human mRNA for DNA binding protein TAXREB67, D83777 Human mRNA for KIAA0193 gene, complete cds, U42031 Human 54 kD progesterone receptor-associated immunophilin FKBP54 mRNA, partial, M80244 Human E16 mRNA, complete cds, 134. D31883 Human mRNA for KIAA0059 gene, complete cds, J04444 Human cytochrome c-1 gene, complete cds, M38258 Human retinoic acid receptor gamma 1 mRNA, complete cds, M95787 Human 22 kD smooth muscle protein (SM22) mRNA, complete cds, U00968 Human SREBP-1 mRNA, complete cds, K03195 Human (HepG2) glucose transporter gene mRNA, complete cds, X92720 H. sapiens mRNA for phosphoenolpyruvate carboxykinase, X77366 H. sapiens HBZ17 mRNA, U53347 Human neutral amino acid transporter B mRNA, complete cds, X80695 H. sapiens OXA1Hs mRNA, J04102 Human erythroblastosis virus oncogene homolog 2 (ets-2) mRNA, complete cds, S75762 Oncogene Tls/Chop, Fusion Activated, U14550 Human sialyltransferase SThM (sthm) mRNA, complete cds, L09229 Human long-chain acyl-coenzyme A synthetase (FACL1) mRNA, complete cds, X76534 H. sapiens NMB mRNA, M55268 Human casein kinase II alphaxe2x80x2 subunit mRNA, complete cds, M27396 Human asparagine synthetase mRNA, complete cds, U37519 Human aldehyde dehydrogenase (ALDH8) mRNA, complete cds, X69111 H. sapiens HLH 1R21 mRNA for helix-loop-helix protein, M77836 Human pyrroline 5-carboxylate reductase mRNA, complete cds, D32050 Human mRNA for alanyl-tRNA synthetase, complete cds, X01630 Human mRNA for argininosuccinate synthetase. This group of ultraviolet radiation-regulated polynucleotides is hereinafter referred to as the xe2x80x9crepressed response groupxe2x80x9d of ultraviolet radiation-regulated polynucleotides.
In one embodiment thereof, the composition of matter is a gene array suitable for monitoring gene expression. In one embodiment, the gene array is a low density gene array. In another embodiment, the gene array is a high density gene array. Polynucleotides utilized in the construction of the low or high density gene array include genomic clones, cDNAs, oligonucleotides, and the like.
In accordance with another aspect of the invention, there are provided pharmaceutical compositions for modulating the response of a cell to ultraviolet radiation exposure. The pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure and a pharmaceutically acceptable carrier. The response of the cell to ultraviolet radiation comprises a pattern of expression comprising at least one of the following: a first response group, a second response group, and a third response group. In one embodiment, the first response group comprises altered expression of at least one nucleic acid molecule encoding a transcription factor protein, at least one nucleic acid molecule encoding a signal transducing protein, and at least one nucleic acid molecule encoding a mitochondrial protein. The second response group comprises altered expression of at least one nucleic acid molecule encoding a secreted growth factor, at least one nucleic acid molecule encoding a cytokine, and at least one nucleic acid molecule encoding a chemokine. The third response group comprises altered expression of at least one nucleic acid molecule encoding an actin-binding protein, at least one nucleic acid molecule encoding a desmosomal protein, at least one nucleic acid molecule encoding a tubulin protein, at least one nucleic acid molecule encoding a cornified envelope protein.
These groups are hereinafter referred to as the xe2x80x9cprimary first response group,xe2x80x9d the xe2x80x9cprimary second response group,xe2x80x9d and the xe2x80x9cprimary third response group,xe2x80x9d respectively.
In other embodiments thereof, the pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response comprising a pattern of expression comprising at least one of the following: (1) the primary first response group; or (2) the primary second response group; or (3) the primary third response group. In other embodiments, the pattern comprises the primary first response group and the primary second response group. In another embodiment, the pattern comprises the primary first response group and the primary third response group. In yet another embodiment, the response comprises the primary second response group and the primary third response group. In still another embodiment, the response comprises the primary first response group, the primary second response group, and the primary third response group.
Additional embodiments of the invention provide pharmaceutical compositions comprising a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm, or ultraviolet radiation energy at a wavelength from about 290 nm to about 320 nm, or ultraviolet radiation energy at a wavelength from about 320 to about 440 nm, or a total ultraviolet radiation energy exposure in the range from about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide a pharmaceutical formulation to modulate the response of a cell that is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell.
In yet another embodiment, the pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure and a pharmaceutically acceptable carrier, wherein the response comprises a pattern of expression comprising at least one of the following: a first response group, a second response group, and a third response group. The first response group comprises at least one polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of. M62831 Human transcription factor ETR101 mRNA, complete cds, X68277 H. sapiens CL 100 mRNA for protein tyrosine phosphatase, L04731 H. sapiens translocation T(4:11) of ALL-1 gene to chromosome 4, X56681 Human junD mRNA, U20734 Human transcription factor junB (junB) gene, 5xe2x80x2 region and complete cds, L38951 H. sapiens importin beta subunit mRNA, complete cds, D87071 Human mRNA for KIAA0233 gene, complete cds, M72885 Human GOS2 gene, 5xe2x80x2 flank and cds, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, S81914 IEX-1=radiation-inducible immediate-early gene [human, placenta, mRNA Partial, U72649 Human BTG2 (BTG2) mRNA, complete cds, D86988 Human mRNA for KIAA0221 gene, complete cds, L19779 H. sapiens histone H2A.2 mRNA, complete cds, U62317 Chromosome 22q13 BAC Clone CIT987SK-384D8 complete sequence, X04412 Human mRNA for plasma gelsolin L27706 Human chaperonin protein (Tcp20) gene complete cds, X61123 Human BTG1 mRNA, M60974growth arrest and DNA-damage-inducible protein (gadd45) mRNA, complete cds, L19437 Human transaldolase mRNA containing transposable element, complete cds, X57985 H. sapiens genes for histones H2B1.1 and H2A, D90086 Human pyruvate dehydrogenase (EC 1.2.4.1) beta subunit gene, exons 1-10, M34182 Human testis-specific protein kinase gamma-subunit mRNA, complete cds, L16862 H. sapiens G protein-coupled receptor kinase (GRK6) mRNA, complete cds, D13705 Human mRNA for fatty acids omega-hydroxylase (cytochrome P-450HKV), complete cd, U37122 Human adducin gamma subunit mRNA, complete cds, D45906 H. sapiens mRNA for LIMK-2, complete cds, U07664 Human HB9 homeobox gene, exons 2 and 3 and complete cds, D87438 Human mRNA for KIAA0251 gene, partial cds, L37042 H. sapiens casein kinase I alpha isoform (CSNK1A1) mRNA, complete cds, D14043 Human mRNA for MGC-24, complete cds, D13988 Human rab GDI mRNA, complete cds, U28480 Uncoupling Protein Uc, D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, M55265 Human casein kinase II alpha subunit mRNA, complete cds, M96803 Human general beta-spectrin (SPTBN1) mRNA, complete cds, U89336 Human HLA class III region containing NOTCH4 gene, partial sequence, homeobox P, D87442 Human mRNA for KIAA0253 gene, partial cds, J03161 Human serum response factor (SRF) mRNA, complete cds, D8965 Human mRNA for KIAA0210 gene, complete cds, U17327 Human neuronal nitric oxide synthase (NOS1) mRNA, complete cds, D86966 Human mRNA for KIAA0211 gene, complete cds, D85527 H. sapiens mRNA for LIM domain, partial cds, U42031 Human 54 kD progesterone receptor-associated immunophilin FKBP54 mRNA, partial, X59434 Human rohu mRNA for rhodanese, M13929 Human c-myc-P64 mRNA, initiating from promoter P0, (HLmyc2.5) partial cds, J05211 Desmoplakin.
The second response group of this embodiment comprises at least one polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of: M57731 Human gro-beta mRNA, complete cds, S81914 EX-1=radiation-inducible immediate-early gene [human, placenta, mRNA Partial, 1, Y00787 Human mRNA for MDNCF (monocyte-derived neutrophil chemotactic factor), XS4489 Human gene for melanoma growth stimulatory activity (MGSA), M72885 Human GOS2 gene, 5xe2x80x2 flank and cds, M62831 Human transcription factor ETR101mRNA, complete cds, M28130 Human interleukin 8 (IL8) gene,.complete cds, X57985 H. sapiens genes for histones H2B.1 and H2A, X53800 Human mRNA for macrophage inflammatory protein-2beta (MIP2beta), L19779 H. sapiens histone H2A.2 mRNA, complete cds, AP001294 H. sapiens IPL (IPL) mRNA, complete cds, X56681 Human junD mRNA, S75762 Oncogene Tls/Chop, Fusion Activate, M84739 Human autoantigen calreticulin mRNA, complete cds, M21302 Human small proline rich protein (sprII) mRNA, clone 174N, V00599 Tubulin, Bet, X70326 Macmarck, D10923 Human mRNA for HM74, D64142 Human mRNA for histone H1x, complete cds, D86974 Human mRNA for KIAA0220 gene, partial cds, M60974 Human growth arrest and DNA-damage-inducible protein (gadd45) mRNA, complete cds, X68277 H. sapiens CL 100 mRNA for protein tyrosine phosphatase, L13391 Human helix-loop-helix basic phosphoprotein (G0S8) gene, complete cds, M31627 Human X box binding protein-1 (XBP-1) mRNA, complete cds, U40369 Human spermidine/spermine N1-acetyltransferase (SSAT) gene, complete cds, X52560 Nuclear Factor Nf-I1, X61123 Human BTG1 mRNA, U20734 Human transcription factor junB (junB) gene, 5xe2x80x2 region and complete cds, U35048 Human TSC-22 protein mRNA, complete cds, M69043 H. sapiens MAD-3 mRNA encoding IkB-like activity, complete cds, X51345 Human jun-B mRNA for JUN-B protein, S68616 Na+/H+ exchanger NHE-1 isoform [human, heart, mRNA, 4516 nt], X89750 H. sapiens mRNA for TGIF protein, X69111 H. sapiens HLH 1R21 mRNA for helix-loop-helix protein, U14603 Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, X52541 Human mRNA for early growth response protein 1 (hEGR1), D50683 H. sapiens mRNA for TGF-betaIIR alpha, complete cds, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, X91247 H. sapiens mRNA for thioredoxin reductase, U05875 Human clone pSK1 interferon gamma receptor accessory factor-1 (AF-1) mRNA, comp, L19314 Human HRY gene, complete cds, M30703 Human amphiregulin (AR) gene, exon 6, clones lambda-ARH(6,12), U34252 Human gamma-aminobutyraldehyde dehydrogenase mRNA, complete cds, S78825 Id1, D85429 H. sapiens gene for heat shock protein 40, complete cds, U41766 Human metalloprotease/disintegrin/cysteine-rich protein precursor (MDC9) mRNA, U89336 Human HLA class III region containing NOTCH4 gene, partial sequence, homeobox PB, M69181 Human nonmuscle myosin heavy chain-B (MYH10) mRNA, partial cds, D15050 Human mRNA for transcription factor AREB6, complete cds, U28386 Human nuclear localization sequence receptor hSRP1alpha mRNA, complete cds, L77886 Human protein tyrosine phosphatase mRNA, complete cds, X64330 H. sapiens mRNA for ATP-citrate lyase, U37122 Human adducin gamma subunit mRNA, complete cds, X74008 H. sapiens mRNA for protein phosphatase 1 gamma, U60205 Human methyl sterol oxidase (ERG25) mRNA, complete cds, X76534 H. sapiens NMB mRNA, D87071 Human mRNA for KIAA0233 gene, complete cds, U90716 Human cell surface protein HCAR mRNA, complete cds, M91083 Human DNA-binding protein (HRC1) mRNA, complete cds, U29607 Human methionine aminopeptidase mRNA, complete cds, M76482 Human 130-kD pemphigus vulgaris antigen mRNA, complete cds, U72066 H. sapiens CtBP interacting protein CtIP (CtIP) mRNA, complete cds, K03195 Human (HepG2) glucose transporter gene mRNA, complete cds, X12953 Human rab2 mRNA, YPT1-related and member of ras family, M60483 Human protein phosphatase 2A catalytic subunit-alpha gene, complete cds, U72649 Human BTG2 (BTG2) mRNA, complete cds, D14520 Human mRNA for GC-Box binding protein BTEB2, complete cds, L08069 Human beat shock protein, E. coli DnaJ homolog mRNA, complete cds, D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, L31801 H. sapiens monocarboxylate transporter 1 (SLC16A1) mRNA, complete cds, S74017 Nrf2=NF-E2-like basic leucine zipper transcriptional activator [human, hemin-in, X87241 H. sapiens mRNA for hFat protein, X52425 Human IL-4-R mRNA for the interleukin 4 receptor, D79994 Human mRNA for KIAA0172 gene, partial cds, M58286 H. sapiens tumor necrosis factor receptor mRNA, complete cds, M13829 Human putative raf related protein (pks/a-raf) mRNA, partial cds, X78992 H. sapiens ERF-2 mRNA, U42031 Human 54 kD progesterone receptor-associated immunophilin FKBP54 mRNA, partial, U88629 Human RNA polymerase II elongation factor ELL2, complete cds, X52611 Human mRNA for transcription factor AP-2, U28749 Human high-mobility group phosphoprotein isoform I-C (HMGIC) mRNA, complete cds, L00058 Human (GH) germline c-myc proto-oncogene, exon 3 and 3xe2x80x2 flank, L26336 Heat Shock Protein, 70 KD (Gb:Y00371, L08246 Human myeloid cell differentiation protein (MCL1) mRNA, S73591 brain-expressed HHCPA78 homolog [human, HL-60 acute promyelocytic, leukemia cells, J05211 Desmoplakin, L00352 Human low density lipoprotein receptor gene, exon 18, Y13647 Stearoyl-Coenzymea Desaturase, X77794 H. sapiens mRNA for cyclin G1, M90656 Human gamma-glutamylcysteine synthetase (GCS) mRNA, complete cds, M13929 Human c-myc-P64 mRNA, initiating from promoter P0, (HLmyc2.5) partial cds, D78129 H. sapiens mRNA for squalene epoxidase, partial cds, X80692 H. sapiens ERK3 mRNA, J00120 Proto-Oncogene C-Myc, Alt. Splice 3, Orf 114.
The third response group of this embodiment comprises at least one polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of: M20030 Human small proline rich protein (sprII) mRNA, clone 930, X53065, M13903 Human involucrin gene, exon 2, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, Alt. Splice, L10343 Human elafin gene, complete cds, M63573 Human secreted cyclophilin-like protein (SCYLP) mRNA, complete cds, M21302 Human small proline rich protein (sprII) mRNA, clone 174N, Y00787 Human mRNA for MDNCF (monocyte-derived neutrophil chemotactic factor), X57985 H. sapiens genes for histones H2B.1 and H2A, L05188 H. sapiens small proline-rich protein 2 (SPRR2B) gene, complete cds, X70326 Macmarcks, X67325 H. sapiens p27 mRNA, L19779 H. sapiens histone H2A.2 mRNA, complete cds, S81914 IEX-1=radiation-inducible immediate-early gene [human, placenta, mRNA Partial 1, D45248 Human mRNA for proteasome activator hPA28 subunit beta, complete cds, Z22548 H. sapiens thiol-specific antioxidant protein mRNA, M22918 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Non-Muscle, Alt. Splice, X06956 Tubulin, Alpha 1, Isoform 44, V00594 Human mRNA for metallothionein from cadmium-treated cells, M80254 H. sapiens cyclophilin isoform (hCyP3) mRNA, complete cds, U04636 Human cyclooxygenase-2 (hCox-2) gene, complete cds, Z14244 H. sapiens coxVIIb mRNA for cytochrome c oxidase subunit VIIb, X99920 H. sapiens mRNA for S100 calcium-binding protein A13, U62800 Human cystatin M (CST6) mRNA, complete cds, L08069 Human heat shock protein, E. coli DnaJ homolog mRNA, complete cds, L20688 Human GDP-dissociation inhibitor protein (Ly-GDI) mRNA, complete cds, M13755 Human interferon-induced 17-kD/15-kD protein mRNA, complete cds, M60278 Human heparin-binding EGF-like growth factor mRNA, complete cds, AF001294 H. sapiens IPL (IPL) mRNA, complete cds, X54489 Human gene for melanoma growth stimulatory activity (MGSA), M21186 Human neutrophil cytochrome b light chain p22 phagocyte b-cytochrome mRNA, compl, D42040 Human mRNA for KIAA9001 gene, complete cds, V00599 Tubulin, Beta, U37690 Human RNA polymerase II subunit (hsRPB10) mRNA, complete cds, M21005 Human migration inhibitory factor-related protein 8 (MRP8) gene, complete cds, M37583 Human histone (H2A.Z) mRNA, complete cds, Z49989 H. sapiens mRNA for smoothelin, L24564 Human Rad mRNA, complete cds, D49824 Human HLA-B null allele mRNA, M59465 Human tumor necrosis factor alpha inducible protein A20 mRNA, complete cds, S54005 thymosin beta-10 [human, metastatic melanoma cell line, mRNA, 453 nt], Z49254 H. sapiens L23-related mRNA, M22919 Myosin, Light Chain, Alkali, Smooth Muscle (Gb:U02629), Smooth Muscle, Alt. Spli, U70660 Human copper transport protein HAH1 (HAH1) mRNA, complete cds, AF006084 H. sapiens Arp2/3 protein complex subunit p41-Arc (ARC41) mRNA, complete cds, X62083 H. sapiens mRNA for Drosophila female sterile homeotic (FSH) homolog, D86974 Human mRNA for KIAA0220 gene, partial cds, M72885 Human GOS2 gene, 5xe2x80x2 flank and cds, S80437 fatty acid synthase {3xe2x80x2 region} [human, breast and HepG2 cells, mRNA Partial, 22, X04654 Human mRNA for U1 RNA-associated 70K protein, t M26311 Human cystic fibrosis antigen mRNA, complete cds, X14850 Human H2A.X mRNA encoding histone H2A.X, M14328 Human alpha enolase mRNA, complete cds, U07919 Human aldehyde dehydrogenase 6 mRNA, complete cds, M28130 Human interleukin 8 (IL8) gene, complete cds, Z21507 H. sapiens EF-1delta gene encoding human elongation factor-1-delta, M92934 Human connective tissue growth factor, complete cds, M27436 Human tissue factor gene, complete cds, with a Alu repetitive sequence in the 3xe2x80x2, X74874 H. sapiens gene for RNA pol II largest subunit, exon 1, X57351 Human 1-8D gene from interferon-inducible gene family, X52979 Human gene for small nuclear ribonucleoproteins SmB and SmBxe2x80x2, U41515 Human deleted in split hand/split foot 1 (DSS1) mRNA, complete cds, D28235 Human PTGS2 gene for prostaglandin endoperoxide synthase-2, complete cds, Y00503 Human mRNA for keratin 19. M57731 Human gro-beta mRNA, complete cds, D50840 H. sapiens mRNA for ceramide glucosyltransferase, complete cds, U52101 Human YMP mRNA, complete cds. D13413 Human mRNA for tumor-associated 120 kD nuclear protein p120, partial cds(carbox, L42379 H. sapiens bone-derived growth factor (BPGF-1) mRNA, complete cds, X52426 H. sapiens mRNA for cytokeratin 13, J04456 Human 14 kD lectin mRNA, complete cds, S78771 NAT=CpG island-associated gene [human, mRNA, 1741 nt], M26730 Human mitochondrial ubiquinone-binding protein (QP) gene, exon 4, U26727 Human p16INK4/MTS1 mRNA, complete cds, X92896 H. sapiens mRNA for ITBA2 protein, Z69043 H. sapiens mRNA translocon-associated protein delta subunit precursor, L76568 H. sapiens excision and cross link repair protein (ERCC4) gene, complete genom, M12125 Human fibroblast muscle-type tropomyosin mRNA, complete cds, U09937 Human urokinase-type plasminogen receptor, exon 7, X15822 Human COX VIIa-L mRNA for liver-specific cytochrome c oxidase (EC 1.9.3.1.), M34516 Human omega light chain protein 14.1 (Ig lambda chain related) gene, exon 3, U53830 H. sapiens interferon regulatory factor 7A mRNA, complete cds, X82693 H. sapiens mRNA for E48 antigen, M58026 Human NB-1 mRNA, complete cds, M90657 Human tumor antigen (L6) mRNA, complete cds, X57579 H. sapiens activin beta-A subunit (exon 2), D38251 Human mRNA for RPB5 (XAP4), complete cds, D89667 H. sapiens mRNA for c-myc binding protein, complete cds, AB000584 H. sapiens mRNA for TGF-beta superfamily protein, complete cds, L76200 Human guanylate kinase (GUK1) mRNA, complete cds, J04794 Human aldehyde reductase mRNA, complete cds, X52882 Human t-complex polypeptide 1 gene, M79463 Human PML-2 mRNA, complete CDS, Y09022 H. sapiens mRNA for Not56like protein, M12529 Human apolipoprotein E mRNA, complete cds, X71129 H. sapiens mRNA for electron transfer flavoprotein beta subunit, X83416 H. sapiens PrP gene, exon 2, D89052 H. sapiens mRNA for proton-ATPase-like protein, complete cds, M60974 Human growth arrest and DNA-damage-inducible protein (gadd45) mRNA, complete cds, M16364 Human creatine kinase-B mRNA, complete cds, D38305 Human mRNA for Tob, complete cds, X87679 Major Histocompatibility Complex, Class I, E (Gb:M21533), Z29505 H. sapiens mRNA for nucleic acid binding protein sub2.3, K02574, U09813 Human mitochondrial ATP synthase subunit 9, P3 gone copy, mRNA, nuclear gene enc, X67951 H. sapiens mRNA for proliferation-associated gene (pag), J04611 Human lupus p70 (Ku) autoantigen protein mRNA, complete cds, U09578 H. sapiens MAPKAP kinase (3 pK) mRNA, complete cds, X53800 Human mRNA for macrophage inflammatory protein-2beta (MIP2beta), V00599 Tubulin, Beta 2, U69126 Human FUSE binding protein 2 (FBP2) mRNA, partial cds, X53416 Human mRNA for actin-binding protein (filamin) (ABP-280), U90546 Human butyrophilin (BTF4) mRNA, complete cds, M58459 Human ribosomal protein (RPS4Y) isoform mRNA, complete eds, M19961 Human cytochrome oxidase subunit Vb (coxVb) mRNA, complete cds, U65579 Human mitochondrial NADH dehydrogenase-ubiquinone Fexe2x80x94S protein 8, 23 kD subunit, X77794 H. sapiens mRNA for cyclin G1, M29064 Human hnRNP B1 protein mRNA, D21853 Human mRNA for KIAA0111 gene, complete cds, X78687 H. sapiens G9 gene encoding sialidase, X15729 Human mRNA for nuclear p68 protein, X04828 Human mRNA for G(i) protein alpha-subunit (adenylate cyclase inhibiting GTP-bind, L27943 H. sapiens cytidine deaminase (CDA) mRNA, complete cds, L40391 H. sapiens (clone s153) mRNA fragment, D42123 H. sapiens mRNA for ESP1/CRP2, complete cds, X74104 H. sapiens mRNA for TRAP beta subunit, M84332 Human ADP-ribosylation factor 1 gene, exons 2-5, L37127 H. sapiens RNA polymerase II mRNA, complete cds, M92843 H. sapiens zinc finger transcriptional regulator mRNA, complete cds, U07664 Human HB9 homeobox gene, exons 2 and 3 and complete cds, L48546 H. sapiens tuberin (TSC2) gene, exons 38, 39, 40 and 41, X53586 Human mRNA for integrin alpha 6, t D21852 Human mRNA for KIAA0029 gene, partial cds, L11066 Human mRNA sequence, J04444 Human cytochrome c-1 gene, complete cds, M95787 Human 22 kD smooth muscle protein (SM22) mRNA, complete cds, L07517 Mucin 6, Gastric (Gb:L07517), X91247 H. sapiens mRNA for thioredoxin reductase, L11672 Human Kruppel related zinc finger protein (HTF10) mRNA, complete cds, U30999 Human (memc) mRNA, 3xe2x80x2UTR, U01337 Human Ser/Thr protein kinase (A-RAF-1) gene, complete cds, U28480 Uncoupling Protein Ucp, X12794 Human v-erbA related ear-2 gene, L22005 Human ubiquitin conjugating enzyme mRNA, partial cds, M12886 Human T-cell receptor active beta-chain mRNA, complete cds, Y08915 H. sapiens mRNA for alpha 4 protein, M24547 Amyloid Beta (A4) Precursor Protein, Alt. Splice 2, A4(751), X76717 H. sapiens MT-11 mRNA, M64347 Human novel growth factor receptor mRNA, 3xe2x80x2 cds, X05409 Human RNA f6r mitochondrial aldehyde dehydrogenase I ALDH I (EC 1.2.1.3), D87469 Human mRNA for KIAA0279 gene, partial cds, M58603 Human nuclear factor kappa-B DNA binding subunit (NF-kappa-B) mRNA, complete cds. M76482 Human 130-kD pemphigus vulgaris antigen mRNA, complete cds, X06323 Human MRL3 mRNA for ribosomal protein L3 homolog (MRL3=mammalian ribosome L, X78992 H. sapiens ERF-2 mRNA, L41351 H. sapiens prostasin mRNA, complete cds, X75342 H. sapiens SHB mRNA, U83115 Human non-lens beta gamma-crystallin like protein (AIM1) mRNA, partial cds, U88629 Human RNA polymerase II elongation factor ELL2, complete cds, S78825 Id1, U28811 Human cysteine-rich fibroblast growth factor receptor (CFR-1) mRNA, complete cds, M58286 H. sapiens tumor necrosis factor receptor mRNA, complete cds, D78129 H. sapiens mRNA for squalene epoxidase, partial cds, D14874 H. sapiens mRNA for adrenomedullin precursor, complete cds, Z26317 H. sapiens mRNA for desmoglein 2, L19267 H. sapiens 59 protein mRNA, 3xe2x80x2 end, J00120 Proto-Oncogene C-Myc, Alt. Splice 3, Orf 114, U33821 Human tax1-binding protein TXBP151 mRNA, complete cds, U52100 Human XMP mRNA, complete cds, L31801 H. sapiens monocarboxylate transporter 1 (SLC16A1) mRNA, complete cds, L00058 Human (GH) germline c-myc proto-oncogene, exon 3 and 3xe2x80x2 flank, U52426 H. sapiens GOK (STIM1) mRNA, complete cds, M80244 Human E16 mRNA, complete cds, U56418 Human lysophosphatidic acid acyltransferase-beta mRNA, complete cds, L38490 H. sapiens ADP-ribosylation factor mRNA, complete cds, U14603 Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, L77886 Human protein tyrosine phosphatase mRNA, complete cds, M38258 Human retinoic acid receptor gamma 1 mRNA, complete cds, X89750 H. sapiens mRNA for TGIF protein, D85429 H. sapiens gene for heat shock protein 40, complete cds, J05211 Desmoplakin I, M31627 Human X box binding protein-1 (XBP-1) mRNA, complete cds, X80695 H. sapiens OXA1Hs mRNA, M54915 Human h-pim-1 protein (h-pim-1) mRNA, complete cds, D83777 Human mRNA for KIAA0193 gene, complete cds, D31883 Human mRNA for KIAA0059 gene, complete cds, U00968 Human SREBP-1 mRNA, complete cds, K03195 Human (HepG2) glucose transporter gene mRNA, complete cds, D86965 Human mRNA for KIAA0210 gene, complete cds, Z30643 H. sapiens mRNA for chloride channel (putative) 2139 bp, D14520 Human mRNA for GC-Box binding protein BTEB2, complete cds, D87462 Human mRNA for KIAA0272 gene, partial cds, X80692 H. sapiens ERK3 mRNA, X90858 H. sapiens mRNA for uridine phosphorylase, M57763 Human ADP-ribosylation factor (hARF6) mRNA, complete cds, X92720 H. sapiens mRNA for phosphoenolpyruvate carboxykinase, M81601 Human transcription elongation factor (SII) mRNA, complete cds, X52611 Human mRNA for transcription factor AP-2, U09587 Human glycyl-tRNA synthetase mRNA, complete cds, U14550 Human sialyltransferase STHM (sthm) mRNA, complete cds, D90209 Human mRNA for DNA binding protein TAXREB67, X77366 H. sapiens HBZ17 mRNA, X76534 H. sapiens NMB mRNA, U37519 Human aldehyde dehydrogenase (ALDH8) mRNA, complete cds, M83667 Human NF-IL6beta protein mRNA, complete cds, U53347 Human neutral amino acid transporter B mRNA, complete cds, L09229 Human long-chain acyl-coenzyme A synthetase (FACL1) mRNA, complete cds, S73591 brain-expressed HHCPA78 homolog [human, HL-60 acute promyelocytic leukemia cells, M13929 Human c-myc-P64 mRNA, initiating from promoter P0, (HLmyc2.5) partial cds, M55268 Human casein kinase II alphaxe2x80x2 subunit mRNA, complete cds, M77836 Human pyrroline 5-carboxylate reductase mRNA, complete cds, HG2724HT2820_at S75762 Oncogene Tls/Chop, Fusion Activated, U72066 H. sapiens CtBP interacting protein CtIP (CtIP) mRNA, complete cds, U42031 Human 54 kD progesterone receptor-associated immunophilin FKBP54 mRNA, partial, M27396 Human asparagine synthetase mRNA, complete cds, X01630 Human mRNA for argininosuccinate synthetase, D32050 Human mRNA for alanyl-tRNA synthetase, complete cds, M90656 Human gamma-glutamylcysteine synthetase (GCS) mRNA, complete cds, J04102 Human erythroblastosis virus oncogene homolog 2 (ets-2) mRNA, complete cds, X69111 H. sapiens HLH 1R21 mRNA for helix-loop-helix protein.
These groups are hereinafter referred to as the xe2x80x9csecondary first response group,xe2x80x9d the xe2x80x9csecondary second response group,xe2x80x9d and the xe2x80x9csecondary third response group,xe2x80x9d respectively.
In another aspect of the invention, pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure and a pharmaceutically acceptable carrier, wherein the response comprises the altered regulation of a protein encoded by a polynucleotide selected from the first response group, second response group, and the third response group. Furthermore, in this embodiment, the first response group comprises altered expression of at least one transcription factor protein, at least one signal transducing protein, and at least one mitochondrial protein. The second response group comprises altered expression of at least one secreted growth factor, at least one cytokine, and at least one chemokine. The third response group comprises altered expression of at least one actin-binding protein, at least one desmosomal protein, and at least one tubulin protein.
These groups are hereinafter referred to as the xe2x80x9ctertiary first response group,xe2x80x9d the xe2x80x9ctertiary second response group,xe2x80x9d and the xe2x80x9ctertiary third response group,xe2x80x9d respectively. Thus, where the primary first, second, and third response groups relate to nucleic acid molecules, the tertiary first, second, and third response groups relate to the proteins encoded by nucleic acid molecules of the primary groups.
In other embodiments thereof, the pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response comprising a pattern of expression comprising at least one of the following: (1) the tertiary first response group; or (2) the tertiary second response group; or (3) the tertiary third response group; or (4) the tertiary first response group and the tertiary second response group; or (5) the tertiary first response group and the tertiary third response group; or (6) the tertiary second response group and the tertiary third response group; or (7) the tertiary first response group and the tertiary second response group and the tertiary third response group.
Additional embodiments thereof provide pharmaceutical compositions comprising a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm, or ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm, or ultraviolet radiation energy at a wavelength of about 320 to about 440 nm, or a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments of the invention provide a pharmaceutical formulation for modulating the expression of a response of a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell, in response to ultraviolet radiation.
In yet another embodiment, the pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response comprising at least one of the following: a first response group; a second response group, and a third response group. In this embodiment, the first response group comprises the altered expression of a plurality of protein molecules, each encoded by a polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of the secondary first response group. The second response group comprises the altered expression of a plurality of protein molecules, each encoded by a polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of the secondary second response group. The third response group comprises the altered expression of a plurality of protein molecules, each encoded by a polynucleotide that is at least 90% identical to a nucleic acid molecule selected from the group consisting of the secondary third response group. These first, second and third response groups are hereinafter referred to as the xe2x80x9cquaternary first response group,xe2x80x9d the xe2x80x9cquaternary second response group,xe2x80x9d and the xe2x80x9cquaternary third response group.xe2x80x9d These groups are, in effect, the protein molecules encoded by the nucleic acid molecules of the secondary first, second and third response groups.
In other embodiments, the pharmaceutical compositions of the invention comprise a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response comprising: (1) the quaternary first response group; or (2) the quaternary second response group; or (3) the quaternary third response group; or (4) the quaternary first response group and the quaternary second response group; or (5) the quaternary first response group and the quaternary third response group; or (6) the quaternary second response group and the quaternary third response group; or (7) the quaternary first response group and the quaternary second response group and the quaternary third response group.
Additional embodiments thereof provide pharmaceutical compositions comprising a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, comprising: (1) ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to about 440 mm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide a therapeutic composition to modulate the response of a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell, to ultraviolet radiation.
Another aspect of the invention provides a pharmaceutical composition for modulating a response of a cell to ultraviolet radiation exposure. This pharmaceutical composition comprises a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response being an altered pattern of expression comprising at least one of the following: the primary first response group, the primary second response group and the primary third response group; and a pharmaceutically acceptable carrier. In embodiments thereof, modulation of the cellular response is an inhibition of the ultraviolet radiation exposure-induced RNA expression or an inhibition of the ultraviolet radiation exposure-repressed RNA expression.
In yet another aspect, the invention provides a pharmaceutical composition for modulating a response of a cell to ultraviolet radiation exposure. This pharmaceutical composition comprises a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response being an altered pattern of expression comprising at least one of the following: a secondary first response group, a secondary second response group, and a secondary third response group.
Another aspect of the invention provides a pharmaceutical composition for modulating a response of a cell to ultraviolet radiation exposure. This pharmaceutical composition comprises a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response being an altered pattern of expression comprising at least one of the following: the tertiary first response group, the tertiary second response group and the tertiary third response group; and a pharmaceutically acceptable carrier. In embodiments thereof, modulation of the cellular response is an inhibition of the ultraviolet radiation exposure-induced protein expression or an inhibition of the ultraviolet radiation exposure-repressed protein expression.
Another aspect of the invention provides a pharmaceutical composition for modulating a response of a cell to ultraviolet radiation exposure. This pharmaceutical composition comprises a compound in sufficient quantity to modulate the response of the cell to ultraviolet radiation exposure, the response being an altered pattern of expression comprising at least one of the following: the quaternary first response group, the quaternary second response group and the quaternary third response group; and a pharmaceutically acceptable carrier. In embodiments thereof, modulation of the cellular response is an inhibition of the ultraviolet radiation exposure-induced protein expression or an inhibition of the ultraviolet radiation exposure-repressed protein expression. In embodiments thereof, modulation of the cellular response is an inhibition of the ultraviolet radiation exposure-induced protein expression or an inhibition of the ultraviolet radiation exposure-repressed protein expression.
Another aspect of the invention provides methods for detecting exposure of a cell to ultraviolet radiation. The method comprises measuring the levels of a plurality of RNA molecules in the cell, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In various embodiments thereof, this pattern of expression comprises a first response group, a second response, and/or a third response. In one embodiment thereof, the first response group is the primary first response group previously described above; the second response is the primary second response previously described above; and the third response is the primary third response previously described above. Other embodiments of this aspect of the invention include the following: (1) the pattern of expression is the primary first response group; or (2) the pattern of expression is the primary second response group; or (3) the pattern of expression is the primary third response group; or (4) the pattern of expression is the primary first response group and the primary second response group; or (5) the pattern of expression is the primary first response group and the primary third response group; or (6) the pattern of expression is the primary second response group and the primary third response group; or (7) the pattern of expression is the primary first response group, the primary second response group, and the primary third response group.
Additional embodiments thereof provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
In another embodiment, the method for detecting exposure of a cell to ultraviolet radiation comprises measuring the levels of a plurality of RNA molecules in the cell for at least one time point, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In this embodiment, the pattern of expression comprises a first response group which is the secondary first response group previously described above; a second response which is the secondary second response previously described above; and a third response which is the primary third response previously described above.
In various embodiments thereof, this pattern of expression comprises a first response group, and/or a second response, and/or a third response. In this embodiment, the first response group is the secondary first response group previously described above; the second response is the secondary second response previously described above; and the third response is the secondary third response previously described above. Embodiments thereof include the following: (1) the pattern of expression is the secondary first response group; or (2) the pattern of expression is the secondary second response group; or (3) the pattern of expression is the secondary third response group; or (4) the pattern of expression is the secondary first response group and the secondary second response group; or (5) the pattern of expression is the secondary first response group and the secondary third response group; or (6) the pattern of expression is the secondary second response group and the secondary third response group; or (7) the pattern of expression is the secondary first response group, the secondary second response group, and the secondary third response group.
Additional embodiments of this aspect of the invention provide detection methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of 220 nm to 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
The invention also provides methods for detecting exposure of a cell to ultraviolet radiation in which the measurement of the level of the plurality of RNA molecules is done by expression array analysis. In this method, RNA is isolated from the cell at a time post-ultraviolet radiation exposure. A test expression array is created through nucleic acid hybridization between a labeled probe complementary to the RNA and an expression array substrate. The test expression array is analyzed to create a test expression array data set, which is then compared to the control expression array data. The levels of the plurality of RNA molecules in the cell is then analyzed to establish a response pattern of the cell the response pattern of a cell exposed to ultraviolet radiation comprising: (i) a first response group comprising altered expression of at least one nucleic acid molecule encoding a transcription factor protein, at least one nucleic acid molecule encoding a signal transducing protein, and at least one nucleic acid molecule encoding a mitochondrial protein; (ii) a second response comprising altered expression of at least one nucleic acid molecule encoding a secreted growth factor, at least one nucleic acid encoding a cytokine, and at least one nucleic acid encoding a chemokine; and/or (iii) a third response comprising altered expression of at least one nucleic acid molecule encoding an actin-binding protein, at least one nucleic acid molecule encoding a desmosomal protein, at least one nucleic acid molecule encoding a tubulin protein, and at least one nucleic acid molecule encoding a cornified envelope protein. If the test expression array data set is substantially similar to the response of a cell to ultraviolet radiation, then the cell was exposed to ultraviolet radiation.
Another aspect of the invention provides other methods for detecting exposure of a cell to ultraviolet radiation. These methods comprise measuring a plurality of protein molecules in the cell, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In various embodiments thereof, this pattern of expression comprises a first response group, a second response, and/or a third response. In one embodiment thereof, the first response group is the tertiary first response group previously described above; the second response is the tertiary second response previously described above; and the third response is the tertiary third response previously described above. Embodiments of this method include the following: (1) the pattern of expression is the tertiary first response group; or (2) the pattern of expression is the tertiary second response group; or (3) the pattern of expression is the tertiary third response group; or (4) the pattern of expression is the tertiary first response group and the tertiary second response group; or (5) the pattern of expression is the tertiary first response group and the tertiary third response group; or (6) the pattern of expression is the tertiary second response group and the tertiary third response group; or (7) the pattern of expression is the tertiary first response group, the tertiary second response group, and the tertiary third response group.
Additional embodiments thereof provide methods in which the cell is exposed to ultraviolet radiation comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments of this aspect of the invention provide methods in which the cell exposed to ultraviolet radiation is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
In another embodiment, the method for detecting exposure of a cell to ultraviolet radiation comprises measuring the levels of a plurality of protein molecules in the cell for at least one time point, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In this embodiment, the pattern of expression comprises a first response group which is the quaternary first response group previously described above; a second response which is the quaternary second response previously described above; and a third a response which is the tertiary third response previously described above.
In other embodiments, the first response group is the quaternary first response group previously described above; the second response is the quaternary second response previously described above; and the third response is the quaternary third response previously described above. In yet another embodiment, the pattern of expression is the quaternary first response group; the pattern of expression is the quaternary second response group; the pattern of expression is quaternary third response group; the pattern of expression is the quaternary first response group and the quaternary second response group; the pattern of expression is the quaternary first response group and the quaternary third response group; the pattern of expression is the quaternary second response group and the quaternary third response group; or the pattern of expression is the quaternary first response group, the quaternary second response group, and the quaternary third response group.
Additional embodiments thereof provide methods in which the ultraviolet radiation exposure comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; ultraviolet radiation energy at a wavelength of about 290 mn to about 320 nm; ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mi/cm2. Other embodiments thereof provide that the cell exposed to ultraviolet radiation is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. In one embodiment, the measurement of the level of the plurality of protein molecules is done by ELISA.
Another aspect of the invention provides a screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The screening method comprises contacting a cell with a compound, exposing the cell to ultraviolet radiation to induce a response of the cell to ultraviolet radiation exposure, and measuring the levels of a plurality of RNA molecules in the cell after ultraviolet radiation exposure, wherein any change in the first, second, and/or third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure. In one embodiment thereof, the response comprises at least one of the following: a first response group that is the primary first response group, a second response that is the primary second response, and a third response that is the primary third response.
In other embodiments thereof, the response, or pattern of expression, comprises the following: (1) the pattern of expression is the primary first response group; or (2) the pattern of expression is the primary second response group; or (3) the pattern of expression is the primary third response group; or (4) the pattern of expression is the primary first response group and the primary second response group; or (5) the pattern of expression is the primary first response group and the primary third response group; or (6) the pattern of expression is the primary second response group and the primary third response group; or (7) the pattern of expression is the primary first response group, the primary second response group, and the primary third response group.
Additional embodiments thereof provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell
In another embodiment, the screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation comprises contacting a cell with a compound, exposing the cell to ultraviolet radiation to induce a response of the cell to ultraviolet radiation exposure, and measuring the levels of a plurality of RNA molecules in the cell after ultraviolet radiation exposure, wherein any change in the first, second, and/or third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure. In this embodiment, the pattern of expression comprises a first response group that is the secondary first response group; a second response that is the secondary second response; and/or a third response that is the secondary third response.
In various embodiments thereof, this pattern of expression comprises a first response group, and/or a second response, and/or a third response. In this embodiment, the first response group is the secondary first response group previously described above; the second response is the secondary second response previously described above; and the third response is the secondary third response previously described above. Embodiments thereof include the following: (1) the pattern of expression is the secondary first response group; or (2) the pattern of expression is the secondary second response group; or (3) the pattern of expression is secondary third response group; or (4) the pattern of expression is the secondary first response group and the secondary second response group; or (5) the pattern of expression is the secondary first response group and the secondary third response group; or (6) the pattern of expression is the secondary second response group and the secondary third response group; or (7) the pattern of expression is the secondary first response group, the secondary second response group, and the secondary third response group.
Additional embodiments of this aspect of the invention provide detection methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of 220 nm to 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
The invention also provides methods for the detection of a compound that modulates a response of a cell to ultraviolet radiation in which the measurement of the level of the plurality of RNA molecules is done by expression array analysis. In this method, RNA is isolated from the cell at a time post-ultraviolet radiation exposure. A test expression array is created through nucleic acid hybridization between a labeled probe complementary to the RNA and an expression array substrate. The test expression array is analyzed to create a test expression array data set, which is then compared to the control expression array data set to identify a modulation response of the exposed cell. Modulation indicates that the compound modulates the response of the cell to ultraviolet radiation. The levels of the plurality of RNA molecules in the cell are then analyzed to establish a response pattern of the cell, the response pattern comprising at least one of the following: a secondary first response group, a secondary second response group, and a secondary third response group.
Another aspect of the invention provides other methods for the detection of a compound that modulates a response of a cell to ultraviolet radiation. These methods comprise measuring a plurality of protein molecules in the cell, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In various embodiments thereof, this pattern of expression comprises a first response group, a second response, and/or a third response. In one embodiment thereof, the first response group is the tertiary first response group previously described above; the second response is the tertiary second response previously described above; and the third response is the tertiary third response previously described above. Embodiments of this method include the following: (1) the pattern of expression is the tertiary first response group; or (2) the pattern of expression is the tertiary second response group; or (3) the pattern of expression is the tertiary third response group; or (4) the pattern of expression is the tertiary first response group and the tertiary second response group; or (5) the pattern of expression is the tertiary first response group and the tertiary third response group; or (6) the pattern of expression is the tertiary second response group and the tertiary third response group; or (7) the pattern of expression is the tertiary first response group, the tertiary second response group, and the tertiary third response group.
Additional embodiments thereof provide methods in which the cell is exposed to ultraviolet radiation comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments of this aspect of the invention provide methods in which the cell exposed to ultraviolet radiation is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell.
In another embodiment, the method for the detection of a compound that modulates a response of a cell to ultraviolet radiation comprises measuring the levels of a plurality of protein molecules in the cell for at least one time point, wherein a pattern of expression is established and the pattern is indicative of ultraviolet radiation exposure. In this embodiment, the pattern of expression comprises a first response group which is the quaternary first response group previously described above; a second response which is the quaternary second response previously described above; and a third response which is the quaternary third response previously described above.
In other embodiments, the first response group is the quaternary first response group previously described above; the second response is the quaternary second response previously described above; and the third response is the quaternary third response previously described above. In yet another embodiment, the pattern of expression is the quaternary first response group; the pattern of expression is the quaternary second response group; the pattern of expression is quaternary third response group; the pattern of expression is the quaternary first response group and the quaternary second response group; the pattern of expression is the quaternary first response group and the quaternary third response group; the pattern of expression is the quaternary second response group and the quaternary third response group; or the pattern of expression is the quaternary first response group, the quaternary second response group, and the quaternary third response group.
Additional embodiments thereof provide methods in which the ultraviolet radiation exposure comprising ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the cell exposed to ultraviolet radiation is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. In one embodiment, the measurement of the level of the plurality of protein molecules is done by ELISA.
Another aspect of the invention provides a screening method for the detection of a compound that simulates a response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound, and measuring a level of at least one RNA molecule in the contacted cell, and determining that the level of at least one RNA molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a first response group that is the primary first response group, a second response that is the primary second response group, and a third response that is the primary third response group. A determination that the level of at least one RNA molecule is substantially similar to the altered expression found in the primary first response group, the primary second response group and/or the primary third response group indicates that the compound simulates the response of the cell to ultraviolet radiation exposure.
In other embodiments of the screening method for the detection of a compound that simulates a response of a cell to ultraviolet radiation exposure include the following: (1) the pattern of expression is the primary first response group; or (2) the pattern of expression is the primary second response group; or (3) the pattern of expression is the primary third response group; or (4) the pattern of expression is the primary first response group and the primary second response group; or (5) the pattern of expression is the primary first response group and the primary third response group; or (6) the pattern of expression is the primary second response group and the primary third response group; or (7) the pattern of expression is the primary first response group, the primary second response group, and the primary third response group.
Additional embodiments thereof provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to about 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or a cell selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
In another embodiment, the screening method for the detection of a compound that simulates a response of a cell to ultraviolet radiation exposure, the method comprises contacting the cell with the compound, and measuring a level of at least one RNA molecule in the contacted cell, and determining that the level of at least one RNA molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a secondary first response group, a secondary second response group, and a secondary third response group.
In other embodiments thereof, this response comprises the following: (1) the pattern of expression is the secondary first response group; or (2) the pattern of expression is the secondary second response group; or (3) the pattern of expression is the secondary third response group; or (4) the pattern of expression is the secondary first response group and the secondary second response group; or (5) the pattern of expression is the secondary first response group and the secondary third response group; or (6) t pattern of expression is the secondary second response group and the secondary third response group; or (7) the pattern of expression is the secondary first response group, the secondary second response group, and the secondary third response group.
Additional embodiments of this aspect of the invention provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of 220 nm to 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm 2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound, and measuring a level of at least one protein molecule in the contacted cell, and determining that the level of at least one protein molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a first response group that is the tertiary first response group, a second response group that is the tertiary second response group, and a third response group that is the tertiary third response group. A determination that the level of at least one protein molecule is substantially similar to the altered expression found in the tertiary first response group, the tertiary second response group and/or the tertiary third response group indicates that the compound simulates the response of the cell to ultraviolet radiation exposure.
In another embodiment, the screening method for the detection of a compound that simulates a response of a cell to ultraviolet radiation exposure, the method comprises contacting the cell with the compound, and measuring a level of at least one protein molecule in the contacted cell, and determining that the level of at least one protein molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a tertiary first response group, a tertiary second response group, and a tertiary third response group.
In other embodiments thereof, this response comprises the following: (1) the pattern of expression is the tertiary first response group; or (2) the pattern of expression is the tertiary second response group; or (3) the pattern of expression is tertiary third response group; or (4) the pattern of expression is the tertiary first response group and the tertiary second response group; or (5) the pattern of expression is the tertiary first response group and the tertiary third response group; or (6) the pattern of expression is the tertiary second response group and the tertiary third response group; or (7) the pattern of expression is the tertiary first response group, the tertiary second response group, and the tertiary third response group.
Additional embodiments of this aspect of the invention provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of 220 nm to 440 nm: or (2) ultraviolet radiation energy at a wavelength of about 290 nm to 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound, and measuring a level of at least one RNA molecule in the contacted cell, and determining that the level of at least one protein molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a first response group that is the quaternary first response group, a second response group that is the quaternary second response group, and a third response group that is the quaternary third response group. A determination that the level of at least one RNA molecule is substantially similar to the altered expression found in the primary first response group, the primary second response group and/or the primary third response group indicates that the compound simulates the response of the cell to ultraviolet radiation exposure.
In another embodiment, the screening method for the detection of a compound that simulates a response of a cell to ultraviolet radiation exposure, the method comprises contacting the cell with the compound, and measuring a level of at least one protein molecule in the contacted cell, and determining that the level of at least one protein molecule is substantially similar to that found in the response of the cell to ultraviolet radiation exposure, the response of the cell characterized by at least one of the following: a quaternary first response group, a quaternary second response group, and a quaternary third response group.
In other embodiments thereof, this response comprises the following: (1) the pattern of expression is the quaternary first response group; or (2) the pattern of expression is the quaternary second response group; or (3) the pattern of expression is quaternary third response group; or (4) the pattern of expression is the quaternary first response group and the quaternary second response group; or (5) the pattern of expression is the quaternary first response group and the quaternary third response group; or (6) the pattern of expression is the quaternary second response group and the quaternary third response group; or (7) the pattern of expression is the quaternary first response group, the quaternary second response group, and the quaternary third response group.
Additional embodiments of this aspect of the invention provide methods in which the ultraviolet radiation exposure of the cell comprises: (1) ultraviolet radiation energy at a wavelength in the range of 220 nm to 440 nm; or (2) ultraviolet radiation energy at a wavelength of about 290 nm to 320 nm; or (3) ultraviolet radiation energy at a wavelength of about 320 to 440 nm; or (4) a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2. Other embodiments thereof provide that the exposed cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell.
In an alternative aspect, the invention provides another method for detecting exposure of a cell to ultraviolet radiation. This method comprises measuring the levels of a plurality of RNA molecules in the cell for at least one time point, wherein an altered pattern of expression is established and is indicative of ultraviolet radiation exposure. This pattern comprises a first response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a transcription factor protein, a nucleic acid molecule encoding a signal transducing protein, and a nucleic acid molecule encoding a mitochondrial protein; a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a secreted growth factor, a nucleic acid molecule encoding a cytokine, and a nucleic acid molecule encoding a chemokine; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding an actin-binding protein, a nucleic acid molecule encoding a desmosomal protein, a nucleic acid molecule encoding a tubulin protein, and at least one nucleic acid molecule encoding a cornified envelope protein.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
The invention also provides an embodiment of the method thereof wherein altered expression comprises an increase or decrease in RNA level. Thus, in one particular embodiment, the expression level of a member of the first response group, and/or second response group, and/or third response group increases. In another embodiment thereof, the expression level of a member of the first response group, and/or second response group, and/or third response group decreases.
The invention also provides another method for detecting exposure of a cell to ultraviolet radiation. This method comprises measuring the levels of a plurality of RNA molecules in the cell for at least one time point, wherein an altered pattern of expression is established and is indicative of ultraviolet radiation exposure. This pattern comprises a first response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary first response group; a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary second response group; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary third response group.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 run; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
The invention also comprises an embodiment of the method thereof wherein altered expression comprises an increase or decrease in RNA level. Thus, in one particular embodiment, the expression level of a member of the first response group, and/or second response group, and/or third response group increases. In another embodiment thereof, the expression level of a member of the first response group, and/or second response group, and/or third response group decreases.
In yet another aspect of the invention, a method is provided for detecting exposure of a cell to ultraviolet radiation comprising measuring the levels of a plurality of RNA molecules in the cell by expression array analysis. This method comprises isolating RNA from the cell post ultraviolet radiation exposure, creating a test expression array through nucleic acid hybridization between a labeled probe complementary to the RNA and an expression array substrate. An analysis of the levels of the plurality of RNA molecules in the cell establishes an expression response pattern of the cell. Exposure of the cell to ultraviolet radiation is indicated by an altered pattern of expression comprising the following: (1) a first response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a transcription factor protein, a nucleic acid molecule encoding a signal transducing protein, and a nucleic acid molecule encoding a mitochondrial protein; (2) a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a secreted growth factor, a nucleic acid molecule encoding a cytokine, and (3) a nucleic acid molecule encoding a chemokine; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding an actin-binding protein, a nucleic acid molecule encoding a desmosomal protein, a nucleic acid molecule encoding a tubulin protein, and at least one nucleic acid molecule encoding a cornified envelope protein.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
The invention also comprises an embodiment of the method thereof wherein altered expression comprises an increase or decrease in RNA level. Thus, in one particular embodiment, the expression level of a member of the first response group, and/or second response group, and/or third response group increases. In another embodiment thereof, the expression level of a member of the first response group, and/or second response group, and/or third response group decreases.
In another embodiment, the method thereof comprises measuring the levels of a plurality of RNA molecules in the cell for at least one time point, wherein an altered pattern of expression is established and is indicative of ultraviolet radiation exposure. This pattern comprises a first response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary first response group; a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary second response group; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary third response group.
In an alternative aspect, the invention provides another method for detecting exposure of a cell to ultraviolet radiation. This method comprises measuring the levels of a plurality of proteins in the cell for at least one time point, wherein an altered pattern of expression is established and is indicative of ultraviolet radiation exposure. This pattern comprises a first response comprising an altered pattern of expression of at least one protein selected from the group consisting of a transcription factor protein, a signal transducing protein, and a mitochondrial protein; a second response comprising an altered pattern of expression of at least one protein selected from the group consisting of a secreted growth factor, a cytokine, and a chemokine; and a third response comprising an altered pattern of expression of at least one protein selected from the group consisting of an actin-binding protein, a desmosomal protein, a tubulin protein, and a cornified envelope protein.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
The invention also comprises an embodiment of the method thereof wherein altered expression comprises an increase or decrease in protein level. Thus, in one particular embodiment, the expression level of a member of the first response group, and/or second response group, and/or third response group increases. In another embodiment thereof, the expression level of a member of the first response group, and/or second response group, and/or third response group decreases.
In another embodiment, the invention provides another method for detecting exposure of a cell to ultraviolet radiation. This method comprises measuring the levels of a plurality of protein molecules in the cell for at least one time point, wherein an altered pattern of expression is established and is indicative of ultraviolet radiation exposure. This pattern comprises a first response comprising an altered pattern of expression of at least one protein that is at least 90% identical to a polypeptide encoded by a polynucleotide selected from the group consisting of the secondary first response group; a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary second response group; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary third response group.
In various embodiments related to a protein expression profile of a cell exposed to ultraviolet radiation, ELISA is used to measure the levels of the plurality of proteins in a cell presumptively exposed to ultraviolet radiation.
Another aspect of the invention relates to a screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound and exposing the cell to ultraviolet radiation to induce the response, the response being an altered pattern of expression comprising the following: (1) a first response comprising the altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a transcription factor protein, a nucleic acid molecule encoding a signal transducing protein, and a nucleic acid molecule encoding a mitochondrial protein; (2) a second response comprising the altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding a secreted growth factor, a nucleic acid molecule encoding a cytokine, and a nucleic acid molecule encoding a chemokine; and (3) a third response comprising for the altered pattern of expression of at least one polynucleotide selected from the group consisting of a nucleic acid molecule encoding an actin-binding protein, a nucleic acid molecule encoding a desmosomal protein, a nucleic acid molecule encoding a tubulin protein, and a nucleic acid molecule encoding a codified envelope protein. Next, the levels of a plurality of RNA molecules in the cell are measured for at least one time point after ultraviolet radiation exposure. A change in the altered pattern of expression of the first response, the second response, and/or the third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure.
In one embodiment of the method thereof, the cell is contacted with the compound in vitro.
In another embodiment of the method thereof, the cell is contacted with the compound in vivo. In other embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
The invention also comprises an embodiment of the method thereof wherein altered expression comprises an increase or decrease in RNA level. Thus, in one particular embodiment, the expression level of a member of the first response group, and/or second response group, and/or third response group increases. In another embodiment thereof, the expression level of a member of the first response group, and/or second response group, and/or third response group decreases.
Another aspect of the invention relates to a screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound and exposing the cell to ultraviolet radiation to induce the response, the response being an altered pattern of expression. This pattern comprises a first response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary first response group; a second response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary second response group; and a third response comprising an altered pattern of expression of at least one polynucleotide selected from the group consisting of the secondary third response group. The levels of a plurality of RNA molecules in the cell are measured for at least one time point after ultraviolet radiation exposure, and a change in the altered pattern of expression of the first response group, the second response group, and/or the third response group indicates that the compound modulates the response of the cell to ultraviolet radiation exposure.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the Lime period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
In yet another aspect of the invention, a screening method is provided for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The method comprises contacting the cell with the compound and exposing the cell to ultraviolet radiation to induce the response, the response being an altered pattern of expression. This method comprises isolating RNA from the cell post ultraviolet radiation exposure, creating a test expression array through nucleic acid hybridization between a labeled probe complementary to the RNA and an expression array substrate, analyzing the test expression array to create a test expression array data set; and comparing the test expression array data set to the response of the cell exposed to ultraviolet radiation in the absence of the drug, the response being an altered pattern of expression comprising the following a primary first response group, a primary second response group, and a primary third response group. A change in the altered pattern of expression of the primary first response, the primary second response, and/or the primary third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure.
In embodiments of the method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell, a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
Other embodiments of the method thereof are included in the invention. For example, in one embodiment, cell contact with the compound is topical contact. In another embodiment, the compound modulates the cellular response by inhibiting ultraviolet radiation-induced RNA expression. In another embodiment, the compound inhibits the ultraviolet radiation-repressed expression. In these latter two embodiments, ultraviolet radiation-induced expression is the xe2x80x9cinduced response groupxe2x80x9d and ultraviolet radiation-repressed expression is the xe2x80x9crepressed response group.xe2x80x9d
Another aspect of the invention relates to a screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The screening method comprises contacting the cell with the compound and exposing the cell to ultraviolet radiation to induce the response, the response being an altered pattern of expression comprising the following: (1) a tertiary first response group, (2) a tertiary second response group, and (3) a tertiary third response group; and measuring the levels of a plurality of RNA molecules in the cell for at least one time point after ultraviolet radiation exposure. A change in the altered pattern of expression of the tertiary first response, the tertiary second response, and/or the tertiary third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure.
In various embodiments of the screening method thereof, the cell is contacted with the compound in vitro or in vivo. In other embodiments of the screening method thereof, the cell is a skin cell (epidermal or dermal), or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the screening method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
In various embodiments related to screening method thereof, ELISA is used to measure the levels of the plurality of proteins in a cell in determining the response of the cell to ultraviolet radiation in the presence and absence of the compound.
Another aspect of the invention relates to a screening method for the detection of a compound that modulates a response of a cell to ultraviolet radiation exposure. The screening method comprises contacting the cell with the compound and exposing the cell to ultraviolet radiation to induce the response, the response being an altered pattern of expression comprising the following: (1) a quaternary first response group, (2) a quaternary second response group, and (3) a quaternary third response group; and measuring the levels of a plurality of RNA molecules in the cell for at least one time point after ultraviolet radiation exposure. A change in the altered pattern of expression of the quaternary first response, the quaternary second response, and/or the quaternary third response indicates that the compound modulates the response of the cell to ultraviolet radiation exposure.
In various embodiments of the screening method thereof, the cell is contacted with the compound in vitro or in vivo. In other embodiments of the screening method thereof, the cell is a skin cell (epidermal or dermal) or the cell is selected from the group consisting of a keratinocyte, a Langerhans cell a melanocyte, and a fibroblast cell. Embodiments of the method also vary by the wavelength of ultraviolet radiation and/or the total amount of ultraviolet radiation to which the cell is exposed. For example, in various embodiments, the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 220 nm to about 440 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength of about 290 nm to about 320 nm; or the ultraviolet radiation exposure comprises ultraviolet radiation energy at a wavelength in the range of about 320 nm to about 440 nm; or the ultraviolet radiation exposure comprises a total ultraviolet radiation energy exposure in the range of about 0.2 mJ/cm2 to about 40 mJ/cm2.
Other embodiments of the screening method thereof vary according to the time period post-ultraviolet radiation exposure defining the first response, second response, and third response. In one embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation. In another embodiment, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation. In another embodiment, the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation. In another embodiment, the first response is from about 0.5 hours to about two hours post-exposure to ultraviolet radiation, the second response is from about four hours to about eight hours post-exposure to ultraviolet radiation, and the third response is from about 16 hours to about 24 hours post-exposure to ultraviolet radiation.
In various embodiments related to screening method thereof, ELISA is used to measure the levels of the plurality of proteins in a cell in determining the response of the cell to ultraviolet radiation in the presence and absence of the compound.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. This screening method comprises contacting the cell with the compound; measuring a level of at least one RNA molecule in the contacted cell; and determining that the level of at least one RNA molecule in the cell after exposure to the compound is substantially similar to the level of the RNA found in the cell in response to ultraviolet radiation exposure, the response of the cell to ultraviolet radiation exposure being characterized by altered expression of the following: a primary first response group, a primary second response group, and a primary third response group. A determination that the level of expression of at least one RNA molecule is substantially similar to the altered expression found for the RNA molecule in the primary first response, the primary second response or the primary third response indicates that the compound simulates exposure of the cell to ultraviolet radiation.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. This screening method comprises contacting the cell with the compound; measuring a level of at least one RNA molecule in the contacted cell; and determining that the level of at least one RNA molecule in the cell after exposure to the compound is substantially similar to the level of the RNA found in the cell in response to ultraviolet radiation exposure, the response of the cell to ultraviolet radiation exposure being characterized by altered expression of the following: a secondary first response group, a secondary second response group, and a secondary third response group. A determination that the level of expression of at least one RNA molecule is substantially similar to the altered expression found for the RNA molecule in the secondary first response, the secondary second response or the secondary third response indicates that the compound simulates exposure of the cell to ultraviolet radiation.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. This screening method comprises contacting the cell with the compound; measuring a level of at least one Protein in the contacted cell; and determining that the level of at least one protein in the cell after exposure to the compound is substantially similar to the level of the protein found in the cell in response to ultraviolet radiation exposure, the response of the cell to ultraviolet radiation exposure being characterized by altered expression of the following: a tertiary first response group, a tertiary second response group, and a tertiary third response group. A determination that the level of expression of at least one protein is substantially similar to the altered expression found for the protein in the tertiary first response group, the tertiary second response group or the tertiary third response group indicates that the compound simulates exposure of the cell to ultraviolet radiation.
Another aspect of the invention provides a screening method for the detection of a compound that simulates the response of a cell to ultraviolet radiation exposure. This screening method comprises contacting the cell with the compound; measuring a level of at least one protein in the contacted cell; and determining that the level of at least one protein in the cell after exposure to the compound is substantially similar to the level of the protein found in the cell in response to ultraviolet radiation exposure, the response of the cell to ultraviolet radiation exposure being characterized by altered expression of the following: a quaternary first response group, a quaternary second response group, and a quaternary third response group. A determination that the level of expression of at least one protein is substantially similar to the altered expression found for the protein in the quaternary first response group, the quaternary second response group or the quaternary third response group indicates that the compound simulates exposure of the cell to ultraviolet radiation.